Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial
BackgroundMany 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...
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| Format: | Article |
| Language: | English |
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JMIR Publications
2021-08-01
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| Series: | JMIR Research Protocols |
| Online Access: | https://www.researchprotocols.org/2021/8/e31183 |
| _version_ | 1797735779660726272 |
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| author | Zahra Moussavi Lisa Koski Paul B Fitzgerald Colleen Millikin Brian Lithgow Mohammad Jafari-Jozani Xikui Wang |
| author_facet | Zahra Moussavi Lisa Koski Paul B Fitzgerald Colleen Millikin Brian Lithgow Mohammad Jafari-Jozani Xikui Wang |
| author_sort | Zahra Moussavi |
| collection | DOAJ |
| description |
BackgroundMany 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.
ObjectiveThe 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.
MethodsThe 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.
ResultsThe 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.
ConclusionsOverall, the study with the same protocol is going as expected with no serious AE or any major protocol deviation.
Trial RegistrationClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815
International Registered Report Identifier (IRRID)DERR1-10.2196/31183 |
| first_indexed | 2024-03-12T13:04:02Z |
| format | Article |
| id | doaj.art-0cd5189d4939416dac097efbe301771f |
| institution | Directory Open Access Journal |
| issn | 1929-0748 |
| language | English |
| last_indexed | 2024-03-12T13:04:02Z |
| publishDate | 2021-08-01 |
| publisher | JMIR Publications |
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| spelling | doaj.art-0cd5189d4939416dac097efbe301771f2023-08-28T18:28:46ZengJMIR PublicationsJMIR Research Protocols1929-07482021-08-01108e3118310.2196/31183Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled TrialZahra Moussavihttps://orcid.org/0000-0001-9202-949XLisa Koskihttps://orcid.org/0000-0002-4135-5567Paul B Fitzgeraldhttps://orcid.org/0000-0003-4217-8096Colleen Millikinhttps://orcid.org/0000-0002-3228-308XBrian Lithgowhttps://orcid.org/0000-0002-4631-9485Mohammad Jafari-Jozanihttps://orcid.org/0000-0002-2147-6337Xikui Wanghttps://orcid.org/0000-0002-4157-396X BackgroundMany 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. ObjectiveThe 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. MethodsThe 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. ResultsThe 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. ConclusionsOverall, the study with the same protocol is going as expected with no serious AE or any major protocol deviation. Trial RegistrationClinicalTrials.gov NCT02908815; https://clinicaltrials.gov/ct2/show/NCT02908815 International Registered Report Identifier (IRRID)DERR1-10.2196/31183https://www.researchprotocols.org/2021/8/e31183 |
| spellingShingle | Zahra Moussavi Lisa Koski Paul B Fitzgerald Colleen Millikin Brian Lithgow Mohammad Jafari-Jozani Xikui Wang Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial JMIR Research Protocols |
| title | Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial |
| title_full | Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial |
| title_fullStr | Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial |
| title_full_unstemmed | Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial |
| title_short | Repeated Transcranial Magnetic Stimulation for Improving Cognition in Alzheimer Disease: Protocol for an Interim Analysis of a Randomized Controlled Trial |
| title_sort | repeated transcranial magnetic stimulation for improving cognition in alzheimer disease protocol for an interim analysis of a randomized controlled trial |
| url | https://www.researchprotocols.org/2021/8/e31183 |
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