Telmisartan to reduce insulin resistance in HIV-positive individuals on combination antiretroviral therapy: the TAILoR dose-ranging Phase II RCT

Background Combination antiretroviral therapy (cART) is the standard for human immunodeficiency virus (HIV) infection treatment but can result in metabolic abnormalities, such as insulin resistance, dyslipidaemia and lipodystrophy, which can increase the risk of cardiovascular disease. Objective The objective of the trial was to evaluate whether or not telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ partial agonist, could reduce insulin resistance in HIV-positive individuals on cART, and affect blood and imaging biomarkers of cardiometabolic disease. Design A Phase II, multicentre, randomised, open-labelled, dose-ranging trial of telmisartan over a period of 48 weeks with an adaptive design comprising two stages was used to identify the optimal dose of telmisartan. Participants were randomised to receive one of the three doses of telmisartan (20, 40 and 80 mg) or no intervention (control). Setting Recruitment was from 19 HIV specialist centres in the UK. Participants A total of 377 patients infected with HIV who met the prespecified inclusion/exclusion criteria. Interventions 20-, 40- and 80-mg tablets of telmisartan. Main outcome measures The primary outcome measure was reduction in the homeostatic model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, at 24 weeks. Secondary outcome measures were changes in plasma lipid profile; Quantitative Insulin Sensitivity Check Index (QUICKI) and revised QUICKI, alternative markers of insulin resistance, plasma adipokines (adiponectin, leptin, interleukin 8, tumour necrosis factor alpha, resistin); high-sensitivity C-reactive protein (hs-CRP); body fat redistribution, as measured by magnetic resonance imaging/proton magnetic resonance spectroscopy; changes in renal markers (albumin-to-creatinine ratio, neutrophil gelatinase-associated lipocalin); and tolerability to telmisartan. Results At the interim analysis, 80 mg of telmisartan was taken forward into the second stage of the study. Baseline characteristics were balanced across treatment arms. There were no differences in HOMA-IR [0.007, standard error (SE) 0.106], QUICKI (0.001, SE 0.001) and revised QUICKI (0.002, SE 0.002) at 24 weeks between the telmisartan (80 mg; n = 106) and non-intervention (n = 105) arms. Longitudinal analysis over 48 weeks showed that there was no change in HOMA-IR, lipid or adipokine levels; however, but there were significant, but marginal, improvements in revised QUICKI [0.004, 95% confidence interval (CI) 0.000 to 0.008] and plasma hs-CRP (–0.222, 95% CI –0.433 to –0.011) over 48 weeks. Substudies also showed a significant reduction in the liver fat content at 24 weeks (1.714, 95% CI –2.787 to –0.642; p = 0.005) and urinary albumin excretion at 48 weeks (–0.665, 95% CI –1.31 to –0.019; p = 0.04). There were no differences in serious adverse events between the telmisartan and control arms. Limitations The patients had modest elevations of HOMA-IR at baseline, and our trial could have been under-powered to detect smaller improvements in insulin resistance over time. Conclusions Using a novel adaptive design, we demonstrated that there was no significant effect of telmisartan (80 mg) on the primary outcome measure of HOMA-IR and some secondary outcomes (plasma lipids and adipokines). Telmisartan did lead to favourable, and biologically plausible, changes of the secondary longitudinal outcome measures: revised QUICKI, hs-CRP, hepatic fat accumulation and urinary albumin excretion. Taken collectively, our findings showed that telmisartan did not reduce insulin resistance in patients infected with HIV on antiretrovirals. Future work The mechanistic basis of adipocyte regulation will be studied to allow for development of biomarkers and interventions. Trial registration Current Controlled Trials ISRCTN51069819. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research partnership.

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TAILoR (TelmisArtan and InsuLin Resistance in Human Immunodeficiency Virus [HIV]): An Adaptive-design, Dose-ranging Phase IIb Randomized Trial of Telmisartan for the Reduction of Insulin Resistance in HIV-positive Individuals on Combination Antiretroviral Therapy

Clinical Infectious Diseases ◽

10.1093/cid/ciz589 ◽

2019 ◽

Vol 70 (10) ◽

pp. 2062-2072 ◽

Cited By ~ 4

Author(s):

Sudeep Pushpakom ◽

Ruwanthi Kolamunnage-Dona ◽

Claire Taylor ◽

Terry Foster ◽

Cath Spowart ◽

...

Keyword(s):

Insulin Resistance ◽

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Primary Outcome ◽

Adaptive Design ◽

Stage Ii ◽

Hiv Positive ◽

Combination Antiretroviral Therapy ◽

Immunodeficiency Virus ◽

Dose Ranging

Abstract Background Combination antiretroviral therapy results in metabolic abnormalities which increase cardiovascular disease risk. We evaluated whether telmisartan reduces insulin resistance in human immunodeficiency virus (HIV)–positive individuals on antiretrovirals. Methods We conducted a multicenter, randomized, open-label, dose-ranging controlled trial of telmisartan. Participants with HIV infection receiving combination antiretroviral therapy were randomized equally to either no intervention (control) or 20, 40, or 80 mg telmisartan once daily. The adaptive design allowed testing of all dose(s) of telmisartan in stage I, with the promising dose(s) being taken into stage II. The primary outcome measure was reduction in homeostasis model assessment of insulin resistance (HOMA-IR) at 24 weeks. Results A total of 377 patients were recruited. In stage I, 48, 49, 47, and 45 patients were randomized to control and 20, 40, and 80 mg telmisartan, respectively (total n = 189). At the interim analysis, 80 mg telmisartan was taken forward into stage II. At the end of stage II (n = 105, control; 106, 80-mg arm), there were no differences in HOMA-IR (estimated effect, 0.007; SE, 0.106) at 24 weeks between the telmisartan (80 mg) and nonintervention arms. Longitudinal analysis over 48 weeks showed no change in HOMA-IR, lipid or adipokine levels. There were significant (P ≤ .05), but marginal, improvements in revised Quantitative Insulin Sensitivity Check Index (QUICKI) (0.004) and plasma hs-CRP (−0.222 mg/L) and reduction in liver fat content (1.714 mean reduction; P = .005). Conclusions No significant effect of telmisartan was demonstrated on the primary outcome (HOMA-IR), but there were marginal improvements with some secondary outcome measures. Further studies in this population are warranted to identify novel strategies for preventing cardiovascular morbidity and mortality. Clinical Trial Registration ISRCTN registry (51069819).

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Day hospital versus intensive out-patient mentalisation-based treatment for borderline personality disorder: multicentre randomised clinical trial

The British Journal of Psychiatry ◽

10.1192/bjp.2019.9 ◽

2019 ◽

Vol 216 (2) ◽

pp. 79-84 ◽

Cited By ~ 4

Author(s):

Maaike L. Smits ◽

Dine J. Feenstra ◽

Hester V. Eeren ◽

Dawn L. Bales ◽

Elisabeth M. P. Laurenssen ◽

...

Keyword(s):

Borderline Personality Disorder ◽

Personality Disorder ◽

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Borderline Personality ◽

Treatment Intensity ◽

Day Hospital ◽

Secondary Outcomes

BackgroundTwo types of mentalisation-based treatment (MBT) have been developed and empirically evaluated for borderline personality disorder (BPD): day hospital MBT (MBT-DH) and intensive out-patient MBT (MBT-IOP). No trial has yet compared their efficacy.AimsTo compare the efficacy of MBT-DH and MBT-IOP 18 months after start of treatment. MBT-DH was hypothesised to be superior to MBT-IOP because of its higher treatment intensity.MethodIn a multicentre randomised controlled trial (Nederlands Trial Register: NTR2292) conducted at three sites in the Netherlands, patients with BPD were randomly assigned to MBT-DH (n = 70) or MBT-IOP (n = 44). The primary outcome was symptom severity (Brief Symptom Inventory). Secondary outcome measures included borderline symptomatology, personality functioning, interpersonal functioning, quality of life and self-harm. Patients were assessed every 6 months from baseline to 18 months after start of treatment. Data were analysed using multilevel modelling based on intention-to-treat principles.ResultsSignificant improvements were found on all outcome measures, with moderate to very large effect sizes for both groups. MBT-DH was not superior to MBT-IOP on the primary outcome measure, but MBT-DH showed a clear tendency towards superiority on secondary outcomes.ConclusionsAlthough MBT-DH was not superior to MBT-IOP on the primary outcome measure despite its greater treatment intensity, MBT-DH showed a tendency to be more effective on secondary outcomes, particularly in terms of relational functioning. Patients receiving MBT-DH and MBT-IOP, thus, seem to follow different trajectories of change, which may have important implications for clinical decision-making. Longer-term follow-up and cost-effectiveness considerations may ultimately determine the optimal intensity of specialised treatments such as MBT for patients with BPD.

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Diagnosis and outcome measures in trials for neoplastic meningitis: a review of the literature and clinical experience

Neurosurgical FOCUS ◽

10.3171/foc.1998.4.6.7 ◽

1998 ◽

Vol 4 (6) ◽

pp. E6 ◽

Cited By ~ 15

Author(s):

Michael J. Glantz ◽

Marc C. Chamberlin ◽

Beverly C. Walters

Keyword(s):

Cerebrospinal Fluid ◽

Outcome Measures ◽

Primary Outcome ◽

Randomized Clinical Trials ◽

Outcome Measure ◽

Clinical Care ◽

Primary Outcome Measure ◽

Neoplastic Meningitis ◽

Review Of The Literature ◽

Cytological Examination

Innovative approaches to the treatment of neoplastic meningitis are being widely tested. Unfortunately, research on diagnostic strategies and outcome measures on which any advances in treatment ultimately depend, has not been avidly pursued. A critical review of the literature on neoplastic meningitis published since 1978 was undertaken by using MEDLINE and other English language databases. All articles addressing the issues of diagnostic or response criteria were included. Randomized clinical trials (RCTs) were emphasized. Prospectively collected data from the authors' institution correlating the results of cerebrospinal fluid (CSF) cytological examinations with Karnofsky Performance Scale (KPS) score are also discussed. Twenty-six studies (representing 1208 patients) fulfilled search criteria. Only three were RCTs. Cerebrospinal fluid cytology was the sole diagnostic criterion in two-thirds of studies. The results of CSF cytological examination alone or in combination with other clinical or laboratory endpoints constituted the primary outcome measure in 85%. Few studies attempted to address known deficiencies in the reliability and validity of these measures, and correlation between measures was poor. Quality of life was never used as a primary outcome measure. All currently available measurements, including CSF cytology, biochemistry, immunological, and molecular markers, neuroimaging studies, clinical examination, and survival, suffer from poor sensitivity and/or specificity, and often correlate poorly with each other. Although CSF cytological examination, performed according to a rigorous, research-supported protocol, may be the optimum diagnostic and outcome measure at this time, additional research is a prerequisite for any further advances in the clinical care of patients with neoplastic meningitis.

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Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review

International Psychogeriatrics ◽

10.1017/s1041610211001116 ◽

2011 ◽

Vol 24 (5) ◽

pp. 689-697 ◽

Cited By ~ 17

Author(s):

P. A. Thompson ◽

D. E. Wright ◽

C. E. Counsell ◽

J. Zajicek

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Statistical Analysis ◽

Statistical Methods ◽

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Primary Analysis

ABSTRACTBackground: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.Methods: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.Results: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.Conclusions: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

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Combining Lovastatin and Minocycline for the Treatment of Fragile X Syndrome: Results From the LovaMiX Clinical Trial

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.762967 ◽

2022 ◽

Vol 12 ◽

Author(s):

Camille Champigny ◽

Florence Morin-Parent ◽

Laurence Bellehumeur-Lefebvre ◽

Artuela Çaku ◽

Jean-François Lepage ◽

...

Keyword(s):

Clinical Trial ◽

Fragile X Syndrome ◽

Outcome Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Fragile X ◽

Combined Therapy ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Global Score

Background: Limited success of previous clinical trials for Fragile X syndrome (FXS) has led researchers to consider combining different drugs to correct the pleiotropic consequences caused by the absence of the Fragile X mental retardation protein (FMRP). Here, we report the results of the LovaMiX clinical trial, the first trial for FXS combining two disease-modifying drugs, lovastatin, and minocycline, which have both shown positive effects when used independently.Aim: The main goals of the study were to assess the safety and efficacy of a treatment combining lovastatin and minocycline for patients with FXS.Design: Pilot Phase II open-label clinical trial. Patients with a molecular diagnostic of FXS were first randomized to receive, in two-step titration either lovastatin or minocycline for 8 weeks, followed by dual treatment with lovastatin 40 mg and minocycline 100 mg for 2 weeks. Clinical assessments were performed at the beginning, after 8 weeks of monotherapy, and at week 20 (12 weeks of combined therapy).Outcome Measures: The primary outcome measure was the Aberrant Behavior Checklist-Community (ABC-C) global score. Secondary outcome measures included subscales of the FXS specific ABC-C (ABC-CFX), the Anxiety, Depression, and Mood Scale (ADAMS), the Social Responsiveness Scale (SRS), the Behavior Rating Inventory of Executive Functions (BRIEF), and the Vineland Adaptive Behavior Scale second edition (VABS-II).Results: Twenty-one individuals out of 22 completed the trial. There were no serious adverse events related to the use of either drugs alone or in combination, suggesting good tolerability and safety profile of the combined therapy. Significant improvement was noted on the primary outcome measure with a 40% decrease on ABC-C global score with the combined therapy. Several outcome measures also showed significance.Conclusion: The combination of lovastatin and minocycline is safe in patients for FXS individuals and appears to improve several elements of the behavior. These results set the stage for a larger, placebo-controlled double-blind clinical trial to confirm the beneficial effects of the combined therapy.

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P07 Identifying the primary outcome measure and protocol components for a prospective feasibility study of corticosteroid regimens for CYP with JIA using consensus methods with young people, families and professionals

Rheumatology ◽

10.1093/rheumatology/kez415.003 ◽

2019 ◽

Vol 58 (Supplement_4) ◽

Author(s):

Simon R. Stones ◽

Heather Bagley ◽

Michael W. Beresford ◽

Ashley Jones ◽

Flora McErlane ◽

...

Keyword(s):

Young People ◽

Outcome Measures ◽

Feasibility Study ◽

Primary Outcome ◽

Outcome Measure ◽

Conflicts Of Interest ◽

Rapid Onset ◽

Primary Outcome Measure ◽

Feasibility Trial ◽

Consensus Methods

Abstract Background Juvenile idiopathic arthritis (JIA) is an umbrella term for seven relapsing-remitting inflammatory conditions in children and young people (CYP). Early, intensive treatment can prevent long-term damage; however, established drugs exhibit a delayed response, prompting the need for rapid-onset treatment in the form of corticosteroids. Given a lack of consensus as to which corticosteroid induction regimen should be used for CYP with JIA, a feasibility trial of different regimens is needed. The aim was to achieve consensus among CYP, families, and healthcare professionals (HCPs) about the primary outcome measures and protocol components to include in a prospective feasibility study. Methods A modified Nominal Group Technique was used to achieve consensus on the most appropriate primary outcome measure to be included in a prospective feasibility study, in addition to other protocol components such as inclusion/exclusion criteria. Fifteen participants participated in the process, including a combination of CYP with JIA, families (n = 9) and HCPs (n = 6). Results In the first vote, participants agreed that Juvenile Arthritis Disease Activity Score (JADAS) and Physician Global Assessment Score were most meaningful. During sub-group discussions, the need for a composite score which captured the voice of CYP and families was emphasised. In the second vote, JADAS and the JIA Core Set were identified as the most important. Further discussions led to the results of the third vote, agreeing JADAS as the primary outcome measure of choice being measured at 6 weeks after commencement of treatment. The majority of HCPs, CYP and families voted for all JIA sub-types to be included in a prospective feasibility study, with some queries about the inclusion of systemic JIA given its unique presentation. Participants also identified the need for more frequent data collection time points to capture the rapid onset of corticosteroid action, while CYP and families opted for accessible mechanisms for participation, such as digital follow-up strategies. Conclusion It is feasible to include CYP, families and HCPs in synthesising complex concepts to agree by consensus the design components of clinical research. The primary outcome measure for inclusion in a prospective feasibility study of corticosteroid regimens in CYP with JIA was co-prioritised, with CYP and families taking a leading role in the ultimate selection of an appropriate outcome measure and other study protocol components. Using consensus methods with CYP, families and HCPs is a systematic and rigorous way in which to select outcome measures that are both meaningful and relevant to everyone involved in the care and treatment of CYP with JIA. Conflicts of Interest The authors declare no conflicts of interest.

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188 The Use of a Group Based Upper Limb Programme in Improving Outcome in Acute Stroke Rehabilitation

Age and Ageing ◽

10.1093/ageing/afz103.111 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii17-iii65

Author(s):

Kerri Donnelly ◽

Enya Mulcahy ◽

Catherine Merrick ◽

Orla Fitzgerald

Keyword(s):

Acute Stroke ◽

Grip Strength ◽

Outcome Measures ◽

Upper Limb ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Secondary Outcome ◽

Dominant Hand ◽

Nine Hole Peg Test

Abstract Background After a stroke 85% of patients experience altered arm function. Current research demonstrates that increasing upper limb rehabilitation results in improved outcomes (Ward et al., 2019). The Graded Repetitive Arm Supplementary Programme (GRASP) group is an established adjunctive therapy in the stroke service. The group provides additional therapy for suitable patients with upper extremity deficits. The group is run jointly by a physiotherapist and an occupational therapist. Patients attend twice weekly for a one hour period in addition to their regular therapy. The GRASP group consists of 3 levels of varying abilities and patients are categorised by their Fugl-Meyer score. Methods A prospective audit was completed in 2019 and data was collected using a word document and excel spread sheet. Standardised outcome measures were completed on admission and discharge to establish upper limb ability. The primary outcome measure was the Fugl-Meyer and the secondary outcome measures were the nine hole peg test and grip strength using the Dynamometer. Results 12 patients attended the GRASP group over this period. 75% were males. The average age was 76 years with the age range from 48-95 years. 58% of patients experienced upper limb weakness in their non-dominant hand. Post intervention data was not obtained for 5 patients due to unforeseeable discharge from the acute setting. Preliminary data to date shows that our primary outcome measure improved in 86% of patients with increases ranging from 2-11 points on the Fugl-Meyer score (Minimally Clinical Important Difference =5points). Our secondary outcome measures demonstrated patients had no change (28%) or an improvement (72%) in grip strength and 100% of patients improved on the time taken to complete the nine hole peg test. Conclusion The GRASP group was found to be effective in improving upper limb outcome measures in an acute stroke inpatient hospital setting.

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A randomized, double-blind, placebo-controlled trial of memantine in a behaviorally enriched sample of patients with moderate-to-severe Alzheimer's disease

International Psychogeriatrics ◽

10.1017/s1041610213000239 ◽

2013 ◽

Vol 25 (6) ◽

pp. 919-927 ◽

Cited By ~ 34

Author(s):

Nathan Herrmann ◽

Serge Gauthier ◽

Neli Boneva ◽

Ole Michael Lemming

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Outcome Measures ◽

Primary Outcome ◽

Controlled Trial ◽

Neuropsychiatric Symptoms ◽

Primary Outcome Measure ◽

Community Dwelling ◽

Secondary Outcome ◽

Double Blind

ABSTRACTBackground: Agitation and aggression in Alzheimer's disease (AD) are amongst the most serious of neuropsychiatric symptoms, and contribute to poor outcomes and worse quality of life. Previous studies have suggested a benefit for memantine on agitation and aggression, but none have examined its efficacy in community-dwelling patients with significant agitation and aggression at baseline, utilizing these behaviors as a primary outcome measure.Methods: Patients with moderate-to-severe AD with Neuropsychiatric Inventory (NPI) total score ≥13 and NPI agitation/aggression score ≥1 were randomized to placebo or 20-mg memantine in a double-blind, 24-week trial. Co-primary outcome measures were behavior, measured by total NPI score, and cognition, using the Severe Impairment Battery (SIB). Secondary outcome measures included global assessment, function and other measures of behavior. This trial was registered as Clinicaltrials.gov: NCT00857649.Results: A total of 369 patients (average age = 75, average MMSE = 12) were randomized to placebo or memantine. The study was prematurely terminated due to recruitment problems. There were no statistically significant differences between memantine and placebo in mean change from baseline in NPI, SIB, or any of the secondary outcome measures. Behavior improved in both groups (total NPI change scores −3.90 ± 1.24 for memantine and −5.13 ± 1.23 for placebo). Memantine was generally well tolerated and patient retention in both treatment arms was good.Conclusions: The study failed to show the superiority of memantine in this sample of patients with moderate-to-severe AD with significant baseline agitation and aggression. Methodological limitations could have contributed to these results.

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Efficacy of a strategy-based intervention on text-level reading comprehension in persons with aphasia: a study protocol for a repeated measures study

BMJ Open ◽

10.1136/bmjopen-2020-048126 ◽

2021 ◽

Vol 11 (7) ◽

pp. e048126

Author(s):

Sarah-Maria Thumbeck ◽

Philipp Schmid ◽

Sophie Chesneau ◽

Frank Domahs

Keyword(s):

Reading Comprehension ◽

Outcome Measures ◽

Repeated Measures ◽

Primary Outcome ◽

Outcome Measure ◽

Primary Outcome Measure ◽

Primary Objective ◽

Secondary Outcome ◽

Waiting Period ◽

Reading Activities

IntroductionAt least 68% of persons with aphasia (PWA) experience reading difficulties. Even though strategy-based interventions are a promising treatment approach for text level reading comprehension deficits in PWA, empirical evidence for their efficacy remains rare. The primary objective of this study is the analysis of the efficacy of a strategy-based intervention on text-level reading comprehension and on reading activities in PWA.Methods and analysisIn a repeated measures trial, 24 PWA will first participate in a waiting period and then in a strategy-based intervention (14 face-to-face-sessions, 60 min each). We will apply two combinations of strategies to treat either the microstructure or the macrostructure, respectively. Participants will be randomly allocated to two parallel groups that will receive these combinations in interchanged sequences. Assessments will be implemented before and after each period as well as 3 and 6 months after the intervention. The primary outcome measure is text-level reading comprehension measured with a German version of the Test de Compréhension de Textes (TCT-D) and represented by the score TCT-D Total . A non-blinded and a blinded rater will evaluate the primary outcome measure. Secondary outcome measures will address specific reading functions, reading activities and cognitive functions. The sample size was determined with an a priori power analysis. For statistical analysis, we will use contrast analyses within repeated measures analysis of variance models. We expect significant improvements in primary and secondary outcome measures during the intervention as compared with changes during the waiting period.Ethics and disseminationThis study was approved by the ethics committee of Deutscher Bundesverband für akademische Sprachtherapie und Logopädie (20–10074-KA-MunmErw+Ko). Results and relevant data will be disseminated in peer-reviewed journals, at conferences and on the Open Science Framework.Trial registration numberDRKS00021411 (see Supplementary Table 1).

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P126 Systematic review of outcome measures used in narcolepsy clinical trials

SLEEP Advances ◽

10.1093/sleepadvances/zpab014.167 ◽

2021 ◽

Vol 2 (Supplement_1) ◽

pp. A62-A62

Author(s):

A Schokman ◽

Y Bin ◽

D Naehrig ◽

J Cheung ◽

K Kairaitis ◽

...

Keyword(s):

Outcome Measures ◽

Primary Outcome ◽

Treatment Effectiveness ◽

Treatment Success ◽

Population Data ◽

Primary Outcome Measure ◽

Measurement Instruments ◽

Health Measurement ◽

Preliminary Results ◽

Randomised Controlled

Abstract Introduction Treatment of the sleep disorder narcolepsy is primarily symptomatic. With limited population data and insufficient systems to capture patient data, a greater emphasis has been placed on the patient perspective in determining satisfaction and treatment success in clinical settings. While Randomised Controlled Trials (RCTs) are considered the gold standard when determining treatment effectiveness, how effectiveness is measured in a narcolepsy population remains unknown. Therefore, we aimed to explore the outcome measures used in narcolepsy RCTs, and further evaluate the adequacy of any self-reported outcome measures used. Methods Electronic databases (MEDLINE, EMBASE, CINAHL, SCOPUS, PSYCHINFO) and clinicaltrials.gov were searched in April 2020, with primary and secondary outcomes extracted from eligible studies. Self-reported outcome measures used at least once as a primary outcome measure were further explored, with validation studies of these systematically searched for (using the above databases) and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias tool. Results We identified 82 published RCTs involving patients with narcolepsy, of which 35 objective and 46 subjective measures were used. Of these, the Maintenance of Wakefulness Test (n=29), Epworth Sleepiness Scale (ESS) (n=14) and Multiple Sleep Latency Test (n=9) were the most frequently selected primary outcome measures. While our analysis of self-reported outcome measures is ongoing, preliminary results suggest that few have been adequately validated in a narcolepsy-specific population. Discussion Our preliminary results identify a high level of heterogeneity between outcome measures used in RCTs, thus difficult to draw conclusions and compare interventions.

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