scholarly journals D-cycloserine modulates breathlessness related brain activity over pulmonary rehabilitation

2021 ◽  
Author(s):  
Sarah Louise Finnegan ◽  
Olivia K Harrison ◽  
Sara Booth ◽  
Andrea Dennis ◽  
Martyn Ezra ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Pulmonary Rehabilitation ◽  
Brain Activity ◽  
Exploratory Analysis ◽  
Self Report ◽  
Secondary Outcome ◽  
Experimental Medicine ◽  
Chronic Obstructive ◽  
Brain Areas ◽  
Double Blind

Rationale: For people with Chronic Obstructive Pulmonary Disease (COPD), improvements in breathlessness from pulmonary rehabilitation are neither long lasting nor guaranteed. Previously, we showed that pulmonary rehabilitation induced brain activity changes akin to those seen in exposure based cognitive behavioural therapies (CBT) in other conditions. D-cycloserine is a partial NMDA-receptor agonist which has been shown to enhance CBT. Objectives: Here, we tested whether D-cycloserine would augment the effects of pulmonary rehabilitation on activity in brain areas that process breathlessness expectation. Methods: 72 participants with mild-to-moderate COPD were recruited to a double-blind experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250mg D-cycloserine or matched placebo, administered 15-30 minutes prior to the first four sessions of pulmonary rehabilitation. Brain functional magnetic resonance imaging, self-report questionnaires and clinical measures of respiratory function were collected at three time points: before, during (2-3 weeks) and after pulmonary rehabilitation (6-8 weeks). Measurements: Primary and secondary outcome measures were difference in mean and voxel-wise brain activity across key brain regions of interest. An exploratory analysis determined the interaction with breathlessness-anxiety. Main results: No difference was observed in either primary or secondary outcome measures. However, in the exploratory analysis, D-cycloserine attenuated the relationship between brain activity and breathlessness-anxiety within prefrontal cortex, superior frontal gyrus and precuneus. Conclusions: The observed effects suggest that D-cycloserine augments pulmonary rehabilitation by dampening reactivity to breathlessness cues in brain areas associated with breathlessness expectation and anxiety. This work highlights the opportunity to test brain-active drugs in the context of augmenting behavioural interventions.

Transcranial Electric And Acoustic Stimulation For Tinnitus: Study Protocol For A Randomized Double-Blind Controlled Trial Assessing The Influence of Combined Transcranial Random Noise And Acoustic Stimulation On Tinnitus Loudness And Distress

2021 ◽  
Author(s):  
Mariana Lopes Martins ◽  
Tobias Kleinjung ◽  
Martin Meyer ◽  
Vitushika Raveenthiran ◽  
Zino Wellauer ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Neuronal Activity ◽  
Treatment Option ◽  
Brain Activity ◽  
Controlled Trial ◽  
Random Noise ◽  
Acoustic Stimulation ◽  
Secondary Outcome ◽  
Double Blind ◽  
Transcranial Random Noise Stimulation

Abstract Background: Tinnitus is the result of aberrant neuronal activity. As a novel treatment form, neuromodulation is used to modify neuronal activity of brain areas involved in tinnitus generation. Among the different forms of electric stimulation, transcranial Random Noise Stimulation (tRNS) has been shown to be a promising treatment option for tinnitus. In addition, recent studies indicate that the reduction in tinnitus can be more pronounced when different modalities of stimulation techniques are combined (“bimodal stimulation”). TRNS can be used in combination with acoustic stimulation (AS), a further treatment option recognized in the literature. The aim of the proposed study is to investigate whether simultaneous tRNS and AS improve levels of tinnitus loudness and distress. Methods: The intervention consists of bilateral HD-tRNS over the auditory cortex combined with the application of AS which is studied in a cross-over design. The visits will be performed in 26 sessions. There will be 20 treatment sessions, divided into two blocks: active and sham HD-tRNS. Within the blocks, the interventions are divided into Group A: HD-tRNS and AS, and Group B: HD-tRNS alone. Furthermore, in addition to the assessments directly following the intervention sessions, there will be six extra sessions performed subsequently at the end of each block, after a period of some days (Follow-ups 1 and 2) and a month after the last intervention (C). Primary outcome measures are analogue scales for evaluation of subjective tinnitus loudness and distress, and the audiological measurement of Minimum Masking Level (MML). Secondary outcome measures are brain activity as measured by electroencephalography and standardized questionnaires for evaluating tinnitus distress and severity. Discussion: To the best of our knowledge, this is the first study, which uses HD-tRNS combined with AS for tinnitus treatment. The cross-over design permits the comparison between HD-tRNS active vs. sham and with vs. without AS. Thus, it will be possible to evaluate the efficacy of the combined approach to HD-tRNS alone. In addition, the use of different objective and subjective evaluations for tinnitus enable more reliable and valid results. Trial registration: Swiss Ethics Committee (BASEC-Nr. 2020-02027); Swiss Federal Complementary Database (kofam.ch: SNCTP000004051); and ClinicalTrials.gov (clinicaltrials.gov: NCT04551404).

Efficacy of a standardised saffron extract (affron®) as an add-on to antidepressant medication for the treatment of persistent depressive symptoms in adults: A randomised, double-blind, placebo-controlled study

2019 ◽  
Vol 33 (11) ◽  
pp. 1415-1427 ◽  
Author(s):  
Adrian L Lopresti ◽  
Stephen J Smith ◽  
Sean D Hood ◽  
Peter D Drummond
Keyword(s):  
Depressive Symptoms ◽  
Outcome Measures ◽  
Short Form ◽  
Self Report ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Persistent Depression ◽  
Saffron Extract

Background: As a stand-alone intervention, saffron has efficacy for the treatment of mild-to-moderate depression. However, research as an adjunct agent is limited. Aims: The effects of saffron as an adjunct to pharmaceutical antidepressants in adults with persistent depression was investigated. Methods: In this eight-week, randomised, double-blind, placebo-controlled study, adults with persistent depression, currently taking a pharmaceutical antidepressant were given a placebo or a saffron extract (affron®, 14 mg b.i.d.). Primary outcome measures included the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS) and self-rated MADRS (MADRS-S). Secondary outcome measures included the Antidepressant Side-Effect Checklist (ASEC) and Short Form-36 Health Survey (SF-36). Results: Of the 160 participants enrolled, 139 provided usable data. Based on the MADRS, depressive symptoms decreased more in participants taking saffron compared with a placebo, with reductions of 41 and 21%, respectively ( p = 0.001). However, scores on the MADRS-S decreased 27 and 26% in the saffron and placebo conditions, respectively ( p = 0.831). Saffron was associated with a greater reduction in adverse effects of antidepressants ( p = 0.019), although this was non-significant after covarying for baseline values ( p = 0.449). Quality of life improved in both groups with no significant between-group differences ( p = 0.638). Conclusion: Adjunctive administration of a standardised saffron extract (affron®) for eight weeks was associated with a greater improvement in depressive symptoms as measured by the clinician-rated MADRS but not the self-report MADRS-S. Given the conflicting results, further research is needed to clarify the clinical benefits of saffron as an adjunctive treatment for adults with persistent depressive symptoms despite antidepressant drug treatment.

scholarly journals Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation

2021 ◽  
Author(s):  
Sarah Louise Finnegan ◽  
Michael Browning ◽  
Eugene Duff ◽  
Catherine J. Harmer ◽  
Andrea Reinecke ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Pulmonary Rehabilitation ◽  
Brain Activity ◽  
Strong Predictor ◽  
Functional Brain Imaging ◽  
Self Report ◽  
Experimental Medicine ◽  
Functional Brain ◽  
Imaging Markers ◽  
Clinical Measures

Background: Chronic breathlessness in COPD is effectively treated with pulmonary rehabilitation. However, baseline patient characteristics predicting improvements in breathlessness are unknown. This knowledge may provide better understanding of the mechanisms engaged in treating breathlessness, helping to individualise therapy. Increasing evidence supports the role of expectation (i.e. placebo and nocebo effects) in breathlessness perception. In this study, we tested functional brain imaging markers of breathlessness expectation as predictors of therapeutic response to pulmonary rehabilitation, and whether D-cycloserine, a brain-active drug known to influence expectation mechanisms, modulates any predictive model. Methods: Data from 72 participants with mild-to-moderate COPD recruited to a randomised double-blind controlled experimental medicine study of D-cycloserine given during pulmonary rehabilitation was analysed (ID: NCT01985750). Baseline variables, including brain-activity, self-report questionnaires responses, clinical measures of respiratory function and drug allocation were used to train machine-learning models to predict the outcome, a minimally clinically relevant change in the dyspnoea-12 score. Findings: Only models that included brain imaging markers of breathlessness-expectation successfully predicted improvements in dyspnoea-12 score (sensitivity 0.88, specificity 0.77). D-cycloserine was independently associated with breathlessness improvement. Models that included only questionnaires and clinical measures did not predict outcome (sensitivity 0.68, specificity 0.2). Interpretation: Brain activity to breathlessness related cues is a strong predictor of clinical improvement in breathlessness over pulmonary rehabilitation. This implies that expectation is key in breathlessness perception. Manipulation of the brain's expectation pathways (either pharmacological or non-pharmacological) merits further testing in the treatment of chronic breathlessness.

scholarly journals Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e029942 ◽  
Author(s):  
Janet Rea Hardy ◽  
Helen Skerman ◽  
Jennifer Philip ◽  
Phillip Good ◽  
David C Currow ◽  
...  
Keyword(s):  
Palliative Care ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Response Rates ◽  
Complete Response ◽  
Response To Treatment ◽  
Secondary Outcome ◽  
Double Blind ◽  
Intention To Treat ◽  
Point Reduction

ObjectivesMethotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.DesignDouble-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.Setting11 palliative care sites in Australia.ParticipantsParticipants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.InterventionsBased on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.Main outcome measuresA ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.ResultsResponse to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In theper protocolanalysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Completeper protocolresponse rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.ConclusionThis study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.Trial registration numberACTRN 12615000177550.

scholarly journals Jiao-tai-wan for insomnia symptoms caused by the disharmony of the heart and kidney: a study protocol for a randomized, double-blind, placebo-controlled trial

2020 ◽  
Author(s):  
Congcong Zeng ◽  
Xi Liu ◽  
Lufeng Hu ◽  
Yuan Feng ◽  
Nengzhi Xia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Outcome Measures ◽  
Study Protocol ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Resonance Spectroscopy ◽  
Double Blind ◽  
Drug Intervention ◽  
Double Blind Placebo ◽  
Insomnia Symptoms

Abstract Background: Insomnia seriously affects people’s normal lives and work. However, effective treatment strategies are scarce. The purpose of this study is to explore the efficacy and safety of Jiao-tai-wan (JTW) for ameliorating insomnia symptoms caused by disharmony of the heart and kidney. Design: This is a randomized, double-blind, placebo-controlled pilot clinical trial. One hundred twenty-four participants suffering from insomnia symptoms will randomly assigned to the JTW or placebo group in an equal ratio. The participants will be asked to take JTW or placebo granules twice a day for 1 week. All data will be gathered at baseline and at the end of drug intervention. The primary outcome measures will be the mean change in the Pittsburgh sleep quality index (PSQI) from baseline to the end of drug intervention. Secondary outcome measures will include the the altered sleep parameters in polysomnography, 1H-magnetic resonance spectroscopy (1H-MRS) evalution, the Disharmony of Heart and Kidney Scoring System score and blood tests, including the levels of serum adenosine and melatonin. A laboratory test will be taken before and after treatment to assess the safety of JTW. Discussion: The outcomes of this study will confirm the efficacy of JTW for the treatment of insomnia symptoms, and will also be used to monitor the safety of JTW. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800019239.Registered on 1st November 2018- Retrospectively registered, http://www.chictr.org.cn/. Keywords: Jiao-tai-wan, Insomnia, Traditional herbal medicine, Randomized controlled trial, Study protocol, Pattern identification Protocol version: Manuscript based on study protocol version 1.3, 1 November 2018.

scholarly journals Breathlessness in COPD: linking symptom clusters with brain activity

2021 ◽  
pp. 2004099
Author(s):  
Sarah L. Finnegan ◽  
Olivia K. Harrison ◽  
Catherine J. Harmer ◽  
Mari Herigstad ◽  
Najib M. Rahman ◽  
...  
Keyword(s):  
Machine Learning ◽  
Functional Neuroimaging ◽  
Brain Activity ◽  
Symptom Burden ◽  
Functional Brain Imaging ◽  
Self Report ◽  
Machine Learning Techniques ◽  
Chronic Obstructive ◽  
Unsupervised Machine Learning ◽  
Learning Techniques

RationaleCurrent models of breathlessness often fail to explain disparities between patients' experiences of breathlessness and objective measures of lung function. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important modulators of breathlessness. Therefore, we have developed a model to better understand the relationships between these factors using unsupervised machine learning techniques. Subsequently we examined how expectation-related brain activity differed between these symptom-defined clusters of participants.MethodsA cohort of 91 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent functional brain imaging, self-report questionnaires and clinical measures of respiratory function. Unsupervised machine learning techniques of exploratory factor analysis and hierarchical cluster modelling were used to model brain-behaviour-breathlessness links.ResultsWe successfully stratified participants across four key factors corresponding to mood, symptom burden and two capability measures. Two key groups resulted from this stratification, corresponding to high and low symptom burden. Compared to the high symptom load group, the low symptom burden group demonstrated significantly greater brain activity within the anterior insula, a key region thought to be involved in monitoring internal bodily sensations (interoception).ConclusionsThis is the largest functional neuroimaging study of COPD to date and is the first to provide a clear model linking brain, behaviour and breathlessness expectation. Furthermore, it was possible to stratify participants into groups, which then revealed differences in brain activity patterns. Together, these findings highlight the value of multi-modal models of breathlessness in identifying behavioural phenotypes, and for advancing understanding of differences in breathlessness burden.

scholarly journals Nicotinamide Riboside as a Neuroprotective Therapy for Glaucoma Study Protocol for a Randomized, Double-blind, Placebo-control Trial

2021 ◽  
Author(s):  
Christopher Kai-shun Leung ◽  
Seraph Tianmin Ren ◽  
Poemen Pui-man Chan ◽  
Kelvin H Wan ◽  
Aziz Kam ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Outcome Measures ◽  
Outcome Measure ◽  
Nerve Degeneration ◽  
Secondary Outcome ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Treatment Groups ◽  
Nicotinamide Riboside ◽  
Optic Nerve Degeneration

Abstract Background Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo. Methods This is a randomized, double blind, placebo controlled, parallel group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models. Discussion Outcome measures in glaucoma neuroprotection trials have been predicated on detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups.

scholarly journals Chinese pediatric Tuina on children with acute diarrhea: study protocol for a randomized sham-controlled trial

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Taoying Lu ◽  
Huiyan Zhang ◽  
Lingjia Yin ◽  
Jianxiong Cai ◽  
Meiling Li ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Acute Diarrhea ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Control Group ◽  
Double Blind ◽  
Pediatric Tuina ◽  
Therapeutic Benefits ◽  
Appropriate Treatment ◽  
Traditional Chinese Medicine Therapy

Abstract Background Acute pediatric diarrhea is one of the most common causes of morbidity and mortality worldwide and seriously affects the health of children. Previous studies have shown that pediatric Tuina, a traditional Chinese medicine therapy, has potential therapeutic benefits for acute pediatric diarrhea. However, the evidence for its effectiveness is insufficient due to the lack of high-quality clinical studies. Our aim is to evaluate the efficacy of Chinese pediatric Tuina for children aged 0–6 years with acute diarrhea. Methods/design This study is a randomized, double-blind, sham-controlled trial. We will include 122 children with acute diarrhea from Dongguan Kanghua Hospital in Guangdong province, China. The patients will be allocated into either the pediatric Tuina group or the sham Tuina group in a 1:1 ratio. The treatment will last for 3 days followed by an 11-day follow-up period. Both groups will receive usual care. In addition, the experimental group will receive 15–25 min of Chinese pediatric Tuina, while the control group will receive 15–25 min of sham pediatric Tuina. Both groups will receive treatments once per day, for 3 consecutive days. Primary outcome measures are diarrhea days from baseline and diarrhea times on the third day. Secondary outcome measures are the global change rating and period of days when the stool character changes to normal. Safety assessments will be monitored during each visit. Discussion This clinical trial is designed to evaluate the efficacy of pediatric Tuina for children with acute diarrhea. We expect results to provide solid evidence and support for pediatric Tuina as an appropriate treatment for children with acute diarrhea. Trial registration ClinicalTrials.gov, NCT03005821. Registered on 29 December 2016.

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