Effect of Insulin Sensitizer Metformin on AD Biomarkers
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- Cognitive Biomarker Outcomes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Alzheimer's Disease Assessment Scale- Cognitive Sub scale (ADAS-COG)
- Neurophysiological Biomarker Outcome [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Cogstate Computerized Psychometric Battery Dementia Severity Rating Scale
- Biochemical Biomarker Outcome [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]Brain MRI (pCASL,MPRAGE and Flair) Lumbar Puncture for CSF
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Metformin
dosage will change during the course of the study. Baseline - 500 mg 1 daily Week 1 - 1000mg 1 2x daily Week 3 - 1500mg 2 daily Week 4 - 2000mg 1 2x daily
Placebo Comparator: Placebo
This is a pilot study using a standard 2X2 randomized, placebo controlled crossover clinical trial to determine the effects of metformin on cognitive, neurophysiological and biochemical biomarkers of AD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01965756
|Contact: Martha Combs, MAemail@example.com|
|Contact: Felicia Greenfield, MSWfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania, Penn Memory Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Patricai Martinez 215-746-2557 email@example.com|
|Contact: Martha Combs 215-615-3084 firstname.lastname@example.org|
|Principal Investigator: Steven E Arnold, MD|
|Principal Investigator:||Steven E Arnold, MD||University of Pennsylvania|