PMID- 34383681 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210903 IS - 1929-0748 (Print) IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 10 IP - 8 DP - 2021 Aug 9 TI - Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial. PG - e31183 LID - 10.2196/31183 [doi] LID - e31183 AB - BACKGROUND: Many clinical trials investigating treatment efficacy require an interim analysis. Recently we have been running a large, multisite, randomized, placebo-controlled, double-blind clinical trial investigating the effect of repetitive transcranial magnetic stimulation (rTMS) treatment for improving or stabilizing the cognition of patients diagnosed with Alzheimer disease. OBJECTIVE: The objectives of this paper are to report on recruitment, adherence, and adverse events (AEs) to date, and to describe in detail the protocol for interim analysis of the clinical trial data. The protocol will investigate whether the trial is likely to reach its objectives if continued to the planned maximum sample size. METHODS: The specific requirements of the analytic protocol are to (1) ensure the double-blind nature of the data while doing the analysis, (2) estimate the predictive probabilities of success (PPoSs), (3) estimate the numbers needed to treat, (4) re-estimate the initial required sample size. The initial estimate of sample size was 208. The interim analysis will be based on 150 patients who will be enrolled in the study and finish at least 8 weeks of the study. Our protocol for interim analysis, at the very first stage, is to determine the response rate for each participant to the treatment (either sham or active), while ensuring the double-blind nature of the data. The blinded data will be analyzed by a statistician to investigate the treatment efficacy. We will use Bayesian PPoS to predict the success rate and determine whether the study should continue. RESULTS: The enrollment has been slowed significantly due to the COVID-19 pandemic and lockdown. Nevertheless, so far 133 participants have been enrolled, while 22 of these have been withdrawn or dropped out for various reasons. In general, rTMS has been found tolerable with no serious AE. Only 2 patients dropped out of the study due to their intolerability to rTMS pulses. CONCLUSIONS: Overall, the study with the same protocol is going as expected with no serious AE or any major protocol deviation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31183. CI - (c)Zahra Moussavi, Lisa Koski, Paul B Fitzgerald, Colleen Millikin, Brian Lithgow, Mohammad Jafari-Jozani, Xikui Wang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.08.2021. FAU - Moussavi, Zahra AU - Moussavi Z AUID- ORCID: 0000-0001-9202-949X AD - Biomedical Engineering Program, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada. AD - Department of Psychiatry, University of Manitoba, Winnipeg, MB, Canada. FAU - Koski, Lisa AU - Koski L AUID- ORCID: 0000-0002-4135-5567 AD - McGill University, Montreal, QC, Canada. FAU - Fitzgerald, Paul B AU - Fitzgerald PB AUID- ORCID: 0000-0003-4217-8096 AD - Department of Psychiatry, Epworth Center for Innovation in Mental Health, Monash University, Melbourne, Australia. FAU - Millikin, Colleen AU - Millikin C AUID- ORCID: 0000-0002-3228-308X AD - Department of Clinical Health Psychology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada. FAU - Lithgow, Brian AU - Lithgow B AUID- ORCID: 0000-0002-4631-9485 AD - Biomedical Engineering Program, Faculty of Engineering, University of Manitoba, Winnipeg, MB, Canada. FAU - Jafari-Jozani, Mohammad AU - Jafari-Jozani M AUID- ORCID: 0000-0002-2147-6337 AD - Department of Statistics & Biomedical Engineering, Faculty of Science, University of Manitoba, Winnipeg, MB, Canada. FAU - Wang, Xikui AU - Wang X AUID- ORCID: 0000-0002-4157-396X AD - Warren Center for Actuarial Studies and Research, The Asper School of Business, University of Manitoba, Winnipeg, MB, Canada. LA - eng SI - ClinicalTrials.gov/NCT02908815 PT - Journal Article DEP - 20210809 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 PMC - PMC8386362 OTO - NOTNLM OT - Alzheimer disease OT - double blind OT - interim analysis, treatment efficacy, repetitive transcranial magnetic stimulation OT - placebo controlled OT - randomized OT - treatment COIS- Conflicts of Interest: PBF is supported by a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (1078567). PBF has received equipment for research from MagVenture A/S, Nexstim, Neuronetics and Brainsway Ltd and funding for research from Neuronetics. He is a founder of TMS Clinics Australia. EDAT- 2021/08/13 06:00 MHDA- 2021/08/13 06:01 PMCR- 2021/08/09 CRDT- 2021/08/12 17:20 PHST- 2021/06/11 00:00 [received] PHST- 2021/06/17 00:00 [accepted] PHST- 2021/06/16 00:00 [revised] PHST- 2021/08/12 17:20 [entrez] PHST- 2021/08/13 06:00 [pubmed] PHST- 2021/08/13 06:01 [medline] PHST- 2021/08/09 00:00 [pmc-release] AID - v10i8e31183 [pii] AID - 10.2196/31183 [doi] PST - epublish SO - JMIR Res Protoc. 2021 Aug 9;10(8):e31183. doi: 10.2196/31183.