Biomarker Qualification for Risk of Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) and Safety and Efficacy Evaluation of Pioglitazone in Delaying Its Onset (TOMMORROW)
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|ClinicalTrials.gov Identifier: NCT01931566|
Recruitment Status : Terminated (Lack of efficacy of the drug; no safety concern)
First Posted : August 29, 2013
Results First Posted : August 14, 2019
Last Update Posted : August 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Mild Cognitive Impairment Due to Alzheimer's Disease||Drug: Pioglitazone Drug: Pioglitazone placebo||Phase 3|
This study has two goals. One of these goals is to see if a new genetic test can determine if participants are at risk of developing Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD) within the next five years. The other goal is to evaluate the study drug called pioglitazone. Pioglitazone is being tested to delay the onset of MCI-AD. This study will look at the effectiveness of pioglitazone in delaying the onset of MCI-AD in cognitively-normal people who are at high-risk of developing MCI-AD, as identified by the biomarker in the non-Hispanic/Latino Caucasian participants.
This multi-centre trial will be conducted worldwide. The study will enroll approximately 3500 subjects. Participants will be assigned to high or low risk groups for developing MCI- AD within the next five years, based on the results of the biomarker risk algorithm. Participants in the high risk group will be randomly assigned to one of the two treatment groups—which will remain unknown to the participant and study doctor during the study (unless there is an urgent medical need):
- Pioglitazone tablet
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient.
Participants in the low risk group will be assigned to placebo. The assignment of each participant to the high or low risk group, as well as the participant's treatment assignment, will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need).
All participants will be asked to take one tablet at the same time each day throughout the study.
The overall time to participate in this study is approximately 5 years. Participants will make up to 14 visits to the clinic, and will be contacted by telephone 3 months after each treatment visit for a follow-up assessment, and 2 weeks after the final visit.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3494 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Simultaneously Qualify a Biomarker Algorithm for Prognosis of Risk of Developing Mild Cognitive Impairment Due to Alzheimer's Disease (MCI Due to AD) and to Test the Safety and Efficacy of Pioglitazone (AD-4833 SR 0.8 mg QD) to Delay the Onset of MCI Due to AD in Cognitively Normal Subjects|
|Actual Study Start Date :||August 1, 2013|
|Actual Primary Completion Date :||July 24, 2018|
|Actual Study Completion Date :||September 6, 2018|
Placebo Comparator: Low Risk Placebo
Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to low risk group for developing MCI-AD for up to 5 years.
Drug: Pioglitazone placebo
Pioglitazone placebo-matching tablets
Placebo Comparator: High Risk Placebo
Pioglitazone placebo-matching tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Drug: Pioglitazone placebo
Pioglitazone placebo-matching tablets
Experimental: High Risk Pioglitazone
Pioglitazone 0.8 mg, sustained release (SR) tablets, orally, once daily to participants assigned to high risk group for developing MCI-AD for up to 5 years.
Pioglitazone SR tablets
- Time to Diagnosis of Mild Cognitive Impairment Due to Alzheimer's Disease (MCI-AD) for Placebo-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, Low-risk, Non-Hispanic/Latino Caucasian Participants [ Time Frame: Baseline to the end of study (approximately up to 5 years) ]The event definition for MCI-AD was the time in days from the randomization date to the date of the first of two consecutive scheduled visits at which a participant was assessed with a diagnosis of MCI due to AD confirmed by adjudication committee. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to the largest event time.
- Time to Diagnosis of MCI Due to AD for Pioglitazone-treated, High-risk, Non-Hispanic/Latino Caucasian Participants Versus Placebo-treated, High-risk, Non-Hispanic/Latino, Caucasian Participants [ Time Frame: Baseline to the end of study (approximately up to 5 years) ]The event definition for MCI-AD was the time in days from the randomization date to the date of the first of two consecutive scheduled visits at which a participant was assessed with a diagnosis of MCI due to AD confirmed by adjudication committee. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to the largest event time.
- Change From Baseline for Cognitive Decline on Composite Score on the Cognitive Test Battery for Pioglitazone-treated Participants Versus Placebo-treated Participants in the High-risk Stratum [ Time Frame: Baseline and Month 48 ]Composite scores derived from the test battery. Domains of Episodic Memory [California Verbal Learning Test-2nd Edition (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R)]; Executive Function [Trail Making Test (TMT) (Part B), Wechsler Adult Intelligence Scale (WAIS)-III Digit Span Test-backwards span]; Language [Multilingual Naming Test (MiNT), Semantic Fluency (animals), Lexical/phonemic fluency (F, A, and S in English; D, S, and F in German)]; and Attention [WAIS-III Digit Span Test-forward span, TMT (Part A)] used for composite score. 12 measures were derived from 8 neuropsychological tests. CVLT-II test involved 2 primary measures (short, long delay recall); BVMT-R had 2 measures (copy and recall); Digit Span and Trail both had 2 measures (forward and backward span and Parts A and B). There was 1 total score for each test: CDT, MINT, semantic and lexical fluency. Total score ranged from -1.222 to 1.707 at baselinbe, a higher composite score indicated better cognition.
- Change From Baseline in Instrumental Activities of Daily Living (Alzheimer's Disease Cooperative Study Activities of Daily Living - Prevention Instrument [ADCS ADL-PI]) Between Pioglitazone-treated and Placebo-treated Groups of the High-risk Stratum [ Time Frame: Baseline and Month 48 ]The ADCS ADL-PI is a functional measure that was specifically designed for standardized administration over long duration clinical studies to prevent AD. The ADCS ADL-PI is a 20-item instrument that included 15 ADL questions, which were scored as 1 (with a lot of difficulty), 2 (with some difficulty), or 3 (as well as usually, with no difficulty), plus 5 vision, hearing, and mobility questions, which were scored from 0 (no) to 1 (yes). ADL Total ranged from 0 to 45, and lower scores indicated greater disability.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01931566
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|Study Director:||Medical Director||Takeda|