Effect of Insulin Sensitizer Metformin on AD Biomarkers
|ClinicalTrials.gov Identifier: NCT01965756|
Recruitment Status : Completed
First Posted : October 18, 2013
Results First Posted : September 21, 2017
Last Update Posted : September 21, 2017
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and other cognitive functions. It is the most common cause of dementia in older adults, affecting approximately 18 million people worldwide, including almost 500,000 in the Philadelphia tri-state area. After age 65, the incidence of AD rises exponentially, doubling every five years. By age 85, almost half of us will have AD. In 2030, as many as 7.7 million Americans could have AD, and by 2050 this number could rise to 11-16 million people. The annual cost of AD in the United States is about $200 billion. AD-related medical complications are among the most common causes of death in the elderly population. Despite these alarming statistics, a "cure" for AD may not be essential since delaying the onset of AD by just 5 years could have a profound impact on this disorder by reducing the incidence and cost of AD by 50% between now and 2050.
AD is difficult to recognize in its earliest stages, in which the principal complaint is typically an increase in episodes of forgetfulness. This stage is now commonly referred to as mild cognitive impairment (MCI). Neuroimaging and CSF biomarkers have demonstrated good accuracy in predicting which MCI patients later "convert" to AD and which tend to remain stable or revert to more normal cognition. The diagnosis of AD itself is made when increased loss of memory and other cognitive abilities (eg, language, praxis, and executive function) affect daily functioning. As the symptoms of dementia inevitably worsen, patients may become incapable of even basic activities such as feeding and dressing themselves. The disease course often spans more than a decade, creating a vast social and financial burden on society and extracting an immeasurable emotional toll on family members.
Clinical and preclinical evidence is accumulating that brain insulin resistance may play a role in the pathogenesis and/or progression of Alzheimer's disease and that ameliorating insulin action in the brain may benefit cognition symptomatically and modify disease pathology.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease Vascular Dementia Dementia Memory Impairment||Drug: Metformin Drug: Placebos||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||This pilot study used a randomized, double-blinded, placebo-controlled 16 week crossover design to examine the effects of metformin on biochemical, neurophysiological, and cognitive biomarkers of AD.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase II Trial to Study the Effect of Metformin on AD Biomarkers: A Randomized Placebo Controlled Crossover Pilot Study of Metformin Effects on Cognitive, Physiological and Biochemical Biomarkers of MCI and Dementia Due to AD|
|Study Start Date :||January 2013|
|Actual Primary Completion Date :||December 22, 2015|
|Actual Study Completion Date :||April 2017|
U.S. FDA Resources
Experimental: Metformin, Then Placebo
Participants first received metformin for 8 weeks, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached. After 8 weeks, subjects were switched to matching placebo for an additional 8 weeks.
|Drug: Metformin Drug: Placebos|
Experimental: Placebo, Then Metformin
Participants first received placebo for 8 weeks. After 8 weeks, subjects were switched to metformin, according to the following dosing schedule: 500 mg by mouth daily for 1 week, then daily dose (in divided doses) increased by 500 mg per week until a maximum of 2000 mg/d (1000mg twice daily) was reached.
|Drug: Metformin Drug: Placebos|
- Word List Memory Total - ADAS-cog [ Time Frame: 16 weeks (total) - measured at baseline, week 8 (crossover), and week 16 ]Alzheimer's Disease Assessment Scale- Cognitive Sub scale (ADAS-COG). Three trials of 10 words each (30 words total)
- Trails-B [ Time Frame: 16 weeks- measured at baseline, week 8 (crossover), and week 16 ]Standard Trails-B assessment, in which subject is asked to begin at Number 1 and draw a line to Letter A, then to Number 2, then to Letter B, then so forth until he/she reaches the END, without lifting their pencil. They should draw the line as fast as possible, and are timed (in seconds).
- Cerebrospinal Fluid Amyloid Beta Concentration [ Time Frame: baseline and 8 weeks ]
- Cerebrospinal Fluid Total Tau Concentration [ Time Frame: baseline and 8 weeks ]
- Cerebrospinal Fluid Phosphorylated Tau Concentration [ Time Frame: baseline and 8 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01965756
|United States, Pennsylvania|
|University of Pennsylvania, Penn Memory Center|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Steven E Arnold, MD||University of Pennsylvania|