MAGDALENA: study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero

IntroductionTen per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy.Methods and analysisMAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9–21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups.Ethics and disseminationThis randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public.Trial registration numberEudraCT2013-004444-31; Pre-results.

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Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial

BMJ Open ◽

10.1136/bmjopen-2020-037700 ◽

2020 ◽

Vol 10 (11) ◽

pp. e037700

Author(s):

Barbara de Barros ◽

Saba M Lambert ◽

Mahesh Shah ◽

Vivek V Pai ◽

Joydeepa Darlong ◽

...

Keyword(s):

Research Ethics ◽

Erythema Nodosum ◽

Controlled Trial ◽

Ethics Committee ◽

Primary Objective ◽

Ethical Review ◽

London School ◽

Double Blind ◽

Research Ethics Committee ◽

Erythema Nodosum Leprosum

IntroductionErythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the ‘MTX and prednisolone study in ENL’ (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL.Methods and analysisMaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients’ reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events.Ethics and disseminationResults will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

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The Effect of An Educational Program for Pregnant Women to Prevent Allergic Diseases In Infants: study protocol for a randomized controlled trial

10.21203/rs.2.9923/v1 ◽

2019 ◽

Author(s):

Rie Ito ◽

Yoko Nezu ◽

Nao Ishiguro ◽

Masato Nakade ◽

Yukiko Ishitsuka ◽

...

Keyword(s):

Pregnant Women ◽

Educational Program ◽

Controlled Trial ◽

Allergic Diseases ◽

Developed Countries ◽

Primary Objective ◽

Allergy Prevention ◽

Prenatal Education ◽

Pediatric Allergy ◽

Randomized Controlled

Abstract Background Allergic diseases in infants have dramatically increased in developed countries during the past few decades. To date, extensive research has been done on risk factors for allergies in infancy, and preventive measures against it. However, the effect of the primary approach to preventing infants' allergy still remains limited. The aim of this trial is to evaluate whether prenatal education interventions, including the latest public research results on allergic diseases, prevent the infant allergies onset. Methods/Design We designed a randomized, controlled, two-arm (standard prenatal education vs our education), parallel-group, assessor-blind, trial. A sample of 120 pregnant women will be recruited at Chiba Aiyukai Kinen hospital and allocation is by computer-generated randomization. Pregnant women in the intervention arm participate in the childbirth education program established by the specialist and a pediatric allergy educator. The program was developed based on evidences supporting interventions on primary prevention, which are suggested to be beneficial to infant’s allergies in recent studies. The primary objective of the study is to determine whether it is possible to establish effective behaviors for allergy prevention during early infancy in pregnant women who participate in an educational program developed by pediatric allergy specialists. Four months after birth, their behaviors will be compared against those of pregnant women who did not participate in the program. Discussion Allergies are common in many individuals worldwide, and can be present from babyhood through the person’s lifetime. One of the strong points of this study is that it will provide pregnant women with accumulated information on preventive knowledge against allergy that can be effective in some cases, and women can apply a combination of these behavior before and after pregnancy. The results of our program will be publicized to help change the behaviors of mothers, and if the program is effective for preventing allergies in infants, it will be disclosed worldwide as a new preventive measure for allergy in infants.

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Parental consent to participation in a randomised trial in children: Associated child, family, and physician factors

Clinical Trials ◽

10.1177/1740774512453219 ◽

2012 ◽

Vol 9 (5) ◽

pp. 645-651 ◽

Cited By ~ 8

Author(s):

Premala Sureshkumar ◽

Patrina Caldwell ◽

Alison Lowe ◽

Judy M Simpson ◽

Gabrielle Williams ◽

...

Keyword(s):

Statistical Power ◽

Research Study ◽

Controlled Trial ◽

Randomised Trial ◽

Vesicoureteric Reflux ◽

Trial Participation ◽

Team Approach ◽

Parental Consent ◽

Study Team ◽

Randomised Controlled

Background Low participation rates in randomised controlled trials involving children are almost a universal problem, leading to high cost and low statistical power. Trial, parent/family, child, and physician factors have been reported to influence parental willingness to consent for paediatric trials. Purpose To identify modifiable and unmodifiable factors associated with parental consent. Methods Demographic and clinical characteristics of children and their families and physician characteristics associated with parental consent were evaluated in a recent randomised placebo-controlled trial of prophylactic antibiotics to prevent recurrent urinary tract infection. Results Of 1109 eligible children identified (mean age, 2.0 years), 412 parents (37.2%) consented. On a multivariate analysis, the only modifiable factor associated with consent was request for consent by a member of the research study team rather than by a member of the clinical team (risk ratio (RR) = 1.9, 95% confidence interval (CI): 1.2–2.9). The unmodifiable factors significantly associated with consent were age of the child (≥4 years) (RR = 1.2, 95% CI: 1.1–1.4), presence of vesicoureteric reflux (RR = 1.5, 95% CI: 1.3–1.8), inpatient management of the index infection (RR = 0.8, 95% CI: 0.7–0.9), and multiple (≥4) symptoms at presentation (RR = 1.3, 95% CI: 1.1–1.5). Limitations We have reported data from only one of the four participating centres in this trial. Data on non-consenters in other participating centres were not completely collected. Data on characteristics of the recruiting physician were limited. These findings are applicable for those considering a single randomised controlled trial. Conclusions Parent, child, and physician factors are associated with consent for trial participation, with most not being modifiable. Having a member of the research study team approach the parent for consent appears to be the only feasible strategy for increasing recruitment to randomised trials in this setting.

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The Effect of Dalteparin on Coagulation Activation during Pregnancy in Women with Thrombophilia: A Randomised Trial.

Blood ◽

10.1182/blood.v108.11.874.874 ◽

2006 ◽

Vol 108 (11) ◽

pp. 874-874

Author(s):

Karim Abou-Nassar ◽

Marc Rodger ◽

Michael J. Kovacs ◽

Steve Doucette ◽

Ramsay Tim ◽

...

Keyword(s):

High Risk ◽

Pregnant Women ◽

Controlled Trial ◽

Randomised Trial ◽

Study Drug ◽

Control Group ◽

Coagulation Activation ◽

Time Points ◽

Box Plots ◽

D Dimer

Abstract Background: Low-molecular weight heparin (LMWH) is increasingly being used for prophylaxis of venous thromboembolism (VTE) and prevention of pregnancy associated morbidity in pregnant women with thrombophilia. Objective: We sought to determine if the administration of prophylactic doses of LMWH down regulates coagulation activation in high risk pregnant women with thrombophilia. Methods: This sub-study was planned as part of a randomized open label controlled trial (Thrombophilia in Pregnancy Prophylaxis Study (TIPPS)) in which patients at high risk of pregnancy complications with confirmed thrombophilia are randomized to receive either dalteparin (5000 units/day until 20 weeks then 5000U q12h until 37 weeks or onset of labor) or no treatment. Blood samples were collected at baseline, day 7–9 (after starting study drug), week 20 (before increasing study drug), week 36 (prior to stopping study drug) and at the time of admission to the labor and delivery unit. Samples were not drawn at fixed times in relation to drug injection. These samples were analyzed for levels of thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2), D-dimer and anti-Xa activity. Generalized linear mixed models were used for statistical analysis and model results were controlled for age, smoking status, type of thrombophilia and predisposing risk factors. The effect of dalteparin on TAT levels was defined as the primary outcome. Results: Of one hundred ninety eight patients eligible, 114 were enrolled in TIPPS. Seventy four were eligible for the TIPPS coagulation activation sub-study and randomized. Twenty-three patients were analyzed in the treatment group (dalteparin) and 28 patients in the control group (no intervention). Levels of coagulation activation factors F1+2, TAT and D-dimer increased significantly throughout pregnancy in both groups (p<0.0001). Dalteparin prophylaxis resulted in a significant increase in anti-Xa activity through pregnancy (p<0.0001) compared to controls. Dalteparin had no significant effects on the levels of TAT, F1+2 and D-dimer throughout pregnancy in thrombophilic women (figure 1). A post hoc Monte Carlo power analysis revealed that our study had over 99% and 64% power to detect reductions in TAT values on treatment of respectively 50% and 25%. Conclusion: Prophylaxis with dalteparin at doses used in this study did not reduce coagulation activation in high risk thrombophilic women during pregnancy. Figure 1 Box plots of TAT levels in high risk pregnant thrombophilic women with (closed boxes) and without (open boxes) dalteparin thromboprophylaxis at different time points during pregnancy. Day 7 represents the time after radomization in TIPPS whereas at other time points represent sepcific gestational ages. The bottom of the boxes mark the 25th percentile, the median lines mark the 50th percentile, the top of the boxes mark the 75th percentile, the bottom and top of the vertical lines mark the 5th and 95th percentile, respectively. Figure 1. Box plots of TAT levels in high risk pregnant thrombophilic women with (closed boxes) and without (open boxes) dalteparin thromboprophylaxis at different time points during pregnancy. Day 7 represents the time after radomization in TIPPS whereas at other time points represent sepcific gestational ages. The bottom of the boxes mark the 25th percentile, the median lines mark the 50th percentile, the top of the boxes mark the 75th percentile, the bottom and top of the vertical lines mark the 5th and 95th percentile, respectively.

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Efficacy of acupuncture versus sham acupuncture or waitlist control for patients with chronic plantar fasciitis: study protocol for a two-centre randomised controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-036773 ◽

2020 ◽

Vol 10 (9) ◽

pp. e036773

Author(s):

Weiming Wang ◽

Sixing Liu ◽

Yan Liu ◽

Zhiwei Zang ◽

Weina Zhang ◽

...

Keyword(s):

Plantar Fasciitis ◽

Controlled Trial ◽

Randomised Trial ◽

Sham Acupuncture ◽

Primary Objective ◽

Control Group ◽

P Value ◽

Waitlist Control ◽

Intention To Treat

IntroductionPlantar fasciitis (PF) is reported to be the most common cause of plantar heel pain. Acupuncture has been used for patients experiencing PF, but evidence of the efficacy of acupuncture on PF is limited. The primary objective of this trial is to compare combined acupuncture and sham acupuncture (SA) versus waitlist control for improving the level of pain experienced by patients suffering from chronic PF.Methods and analysisThis will be a two-centre, parallel-group, sham and no-treatment controlled, assessor-blinded randomised trial. We will randomly allocate 120 participants with chronic PF to acupuncture, SA and waitlist control groups at a ratio of 2:1:1. Participants in the acupuncture and SA groups will receive a 30 min acupuncture or SA treatment for a total of 12 sessions over 4 weeks, with a 12-week follow-up. Participants in the waitlist control group will not undergo treatment for a period of 16 weeks but instead will have the option of 4 weeks (12 sessions) of acupuncture free of charge at the end of the follow-up period. The primary outcome will be the treatment response rate 4 weeks after randomisation, assessed as a minimum of 50% improvement in the worst pain intensity during the first steps in the morning compared with the baseline. All analyses will be performed with a two-sided p value of <0.05 considered significant following the intention-to-treat principle.Ethics and disseminationThe study has been approved by the Ethical Committee of the Guang’anmen Hospital, China Academy of Chinese Medical Sciences (approval no. 2019-210-KY). The results will be disseminated through presentation at a peer-reviewed medical journal, the relevant conferences and scientific meetings.Trial registrationNCT04185259.

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Is integrated private-clinic based early child development care effective? A clustered randomised trial in Pakistan

BJGP Open ◽

10.3399/bjgpopen18x101593 ◽

2018 ◽

Vol 2 (2) ◽

pp. bjgpopen18X101593 ◽

Cited By ~ 2

Author(s):

Muhammad Amir Khan ◽

Syeda Somyyah Owais ◽

Shazia Maqbool ◽

Sehrish Ishaq ◽

Haroon Jehangir Khan ◽

...

Keyword(s):

Child Development ◽

Maternal Depression ◽

Maternal Mental Health ◽

Care Delivery ◽

Controlled Trial ◽

Randomised Trial ◽

Early Child Development ◽

Early Child ◽

Counselling Intervention ◽

Child Age

BackgroundIn Pakistan, high prevalence of delays in early child development (ECD) is associated with poverty and lack of mothers’ caregiving skills. GP clinics, the main sources of care in poor urban localities, lack quality ECD care delivery. A contextualised intervention was developed and tested to enable GPs to deliver clinic-based, tool-assisted ECD counselling of mothers on a quarterly basis.AimTo assess the effectiveness of delivering a contextualised ECD mother-counselling intervention.Design & settingClustered randomised controlled trial, in poor urban localities of Pakistan. Locality clusters were allocated to intervention and control arm using simple randomisation.MethodA total of 2327 mother–child pairs were recruited at 32 GP clinics, one from each cluster-locality; 16 GP clinics per arm. The clinic-based counselling intervention covering child stimulation, nutrition, and maternal mental health was delivered mainly by clinic assistants to mothers at ≤6 weeks, and 3, 6, and 9 months of child age. At 12 months of child age, each mother–child pair was assessed for the primary outcome, that is, delays in the five development domains (determined by Ages and Stages Questionnaire-3 [ASQ-3] score); and secondary outcomes, namely the prevalence of stunting and maternal depression (determined by Patient Health Questionnaire-9 [PHQ-9] score). The outcome assessors were blinded to the cluster–arm allocation. Outcome analyses were calculated on cluster-level.ResultsAt 12 months, the number of children with delay in two or more development domains was significantly lower in the intervention arm (-0.17 [95% confidence interval {CI} = -0.26 to -0.09]; P<0.001) compared to the control arm. The difference in the prevalence of child stunting and maternal depression were also significant at -0.21% (95% CI = -0.30 to -0.13; P<0.001) and -0.23% (95% CI = -0.29 to -0.18; P = 0.000) respectively.ConclusionContextualised ECD care, when delivered at GP clinics in poor urban localities, can effectively reduce the developmental delays during the first 12 months of the child's life.

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The Effect of An Educational Program for Pregnant Women to Prevent Allergic Diseases In Infants: study protocol for a randomized controlled trial

10.21203/rs.2.9923/v3 ◽

2019 ◽

Author(s):

Rie Ito ◽

Yoko Nezu ◽

Nao Ishiguro ◽

Masato Nakade ◽

Yukiko Ishitsuka ◽

...

Keyword(s):

Pregnant Women ◽

Educational Program ◽

Controlled Trial ◽

Allergic Diseases ◽

Developed Countries ◽

Primary Objective ◽

Allergy Prevention ◽

Prenatal Education ◽

Pediatric Allergy ◽

Randomized Controlled

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Prospective randomised trial examining the impact of an educational intervention versus usual care on anticoagulation therapy control based on an SAMe-TT2R2 score-guided strategy in anticoagulant-naïve Thai patients with atrial fibrillation (TREATS-AF): a study protocol

BMJ Open ◽

10.1136/bmjopen-2021-051987 ◽

2021 ◽

Vol 11 (10) ◽

pp. e051987

Author(s):

Arintaya Phrommintikul ◽

Surakit Nathisuwan ◽

Siriluck Gunaparn ◽

Rungroj Krittayaphong ◽

Wanwarang Wongcharoen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Usual Care ◽

Educational Intervention ◽

Controlled Trial ◽

Vitamin K Antagonists ◽

Randomised Trial ◽

Anticoagulation Therapy ◽

Ethical Review ◽

Major Adverse Cardiovascular Events ◽

The Impact

IntroductionThe burden of atrial fibrillation (AF) in Thailand is high and associated with increased morbidity, mortality and healthcare costs. Vitamin K antagonists (eg, warfarin), commonly used for stroke prevention in patients with AF in Thailand, are effective but are often suboptimally controlled. We aim to evaluate the impact of an SAMe-TT2R2 score-guided strategy and educational intervention compared to usual care on anticoagulation control expressed by the time in therapeutic range (TTR) at 12 months, in anticoagulant-naïve Thai patients with AF.Methods and analysisMulticentre, open-label, parallel-group, randomised controlled trial conducted in Thailand among adult patients (age: 18 years) with AF who are anticoagulant naïve. Patients will be randomised to one of two groups; an SAMe-TT2R2 score-guided strategy with educational intervention and usual care versus usual care alone. The planned follow-up period is 12 months. The primary outcome is TTR at 12 months. Secondary outcomes include: (1) TTR at 6 months; (2) thromboembolic and bleeding events at 12 months; (3) composite major adverse cardiovascular events at 12 months; (4) change in patients’ knowledge of AF between baseline and 6 months and 12 months; (5) cost effectiveness; (6) quality of life at baseline, 6 months and 12 months using EQ-5D-5L (Thai version) and (7) patient satisfaction/perceptions of the TREAT intervention. An embedded qualitative study will assess patient perceptions of the TREAT intervention.Ethics and disseminationThe study has been approved by the Ethical Review Committee, Ministry of Public Health of Thailand, and registered in the Thai Clinical Trials Registry. The results of this trial will be submitted for publication in a peer-reviewed journal. Participants will be informed via a link to a preview of the publication. A lay summary will also be provided to all participants prior to publication.Trial registration numberTCTR20180711003.

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Interpersonal counselling versus perinatal-specific cognitive behavioural therapy for women with depression during pregnancy offered in routine psychological treatment services: a phase II randomised trial

BMC Psychiatry ◽

10.1186/s12888-021-03482-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jonathan Evans ◽

Jenny Ingram ◽

Roslyn Law ◽

Hazel Taylor ◽

Debbie Johnson ◽

...

Keyword(s):

Pregnant Women ◽

Cognitive Behavioural Therapy ◽

Health Workers ◽

Psychological Treatment ◽

Randomised Trial ◽

Antenatal Depression ◽

Behavioural Therapy ◽

Low Intensity ◽

Moderate Depression ◽

Cognitive Behavioural

Abstract Background Up to one in eight women experience depression during pregnancy. In the UK, low intensity cognitive behavioural therapy (CBT) is the main psychological treatment offered for those with mild or moderate depression and is recommended during the perinatal period, however referral by midwives and take up of treatment by pregnant women is extremely low. Interpersonal Counselling (IPC) is a brief, low-intensity form of Interpersonal Psychotherapy (IPT) that focuses on areas of concern to service users during pregnancy. To improve psychological treatment for depression during pregnancy, the study aimed to assess the feasibility and acceptability of a trial of IPC for antenatal depression in routine NHS services compared to low intensity perinatal specific CBT. Methods We conducted a small randomised controlled trial in two centres. A total of 52 pregnant women with mild or moderate depression were randomised to receive 6 sessions of IPC or perinatal specific CBT. Treatment was provided by 12 junior mental health workers (jMHW). The primary outcome was the number of women recruited to the point of randomisation. Secondary outcomes included maternal mood, couple functioning, attachment, functioning, treatment adherence, and participant and staff acceptability. Results The study was feasible and acceptable. Recruitment was successful through scanning clinics, only 6 of the 52 women were recruited through midwives. 71% of women in IPC completed treatment. Women reported IPC was acceptable, and supervisors reported high treatment competence in IPC arm by jMHWs. Outcome measures indicated there was improvement in mood in both groups (Change in EPDS score IPC 4.4 (s.d. 5.1) and CBT 4.0 (s.d. 4.8). Conclusions This was a feasibility study and was not large enough to detect important differences between IPC and perinatal specific CBT. A full-scale trial of IPC for antenatal depression in routine IAPT services is feasible. Trial registration This study has been registered with ISRCTN registry 11513120. – date of registration 05/04/2018.

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A Police Partnership Targeting Truancy: Study Protocol for a Cluster Randomised Controlled Trial

Cambridge Journal of Evidence-Based Policing ◽

10.1007/s41887-020-00048-x ◽

2020 ◽

Vol 4 (3-4) ◽

pp. 134-159

Author(s):

Lorraine Mazerolle ◽

Sarah Bennett ◽

Stephanie M. Cardwell

Keyword(s):

School Engagement ◽

Statistical Power ◽

School Attendance ◽

Controlled Trial ◽

Research Question ◽

Randomised Trial ◽

Cluster Randomised Controlled Trial ◽

Cluster Randomised Trial ◽

Cluster Randomised ◽

Randomised Controlled

Abstract Research Question How can an Australian police agency best test its role in a truancy prevention programme that can help to prevent crime? Data Operational and analytic planning for testing the Ability School Engagement Partnership (ASEP) programme in Queensland that aims to increase school attendance and reduce anti-social behaviour, including offending. Methods Fulfilling the requirements for registering a randomised trial protocol with the Clinicaltrials.gov Registry (NCT04281966; date registered 24 February 2020). Findings A protocol deploying a cluster randomised trial offers sufficient statistical power to detect a moderately large effect size as statistically significant with 80% probability. Conclusion Implementation of this protocol as planned would provide an internally valid test of the effectiveness of the ASEP programme in real-world conditions.

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