Phase 2
N=20
Effect of Insulin Sensitizer Metformin on AD Biomarkers
Alzheimer's Disease · Vascular Dementia · Dementia · Memory Impairment
Bottom Line
View on ClinicalTrials.gov: NCT01965756 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
Sep 2017
Primary outcome: Primary: Word List Memory Total - ADAS-cog — 14.35; 14.7; 15.1; 14.67 Words recalled
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Metformin (Drug); Placebos (Drug)
- Age
- Adult, Older Adult · 55+ yrs
- Sex
- All
- Sponsor
- University of Pennsylvania
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Word List Memory Total - ADAS-cog |
14.35; 14.7; 15.1; 14.67; 14.71; 15.5 | — |
| SECONDARY Trails-B |
164.28; 186.7; 164; 170.86; 170.5; 161.8 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- • Ages 55-80.
- 2 Sex distribution: male and female
- Diagnosis of MCI due to AD127 or early dementia due to AD128 with: a) age 55 - 80, b) complaint of cognitive decline, c) abnormal performance on the Logical Memory subtest of the Wechsler Memory Scale, d) MMSE > 21, e) CDR 0.5-1, f) positive topographic (MRI, FDG-PET) or molecular (CSF, amyloid imaging) biomarker consistent with AD, and g) no history of diabetes or other exclusions.
- Fluent in English or Spanish
- Education >5, literate, and/or good working history that precludes consideration of mental retardation
- Visual and auditory acuity sufficient for neuropsychological testing and auditory evoked potential EEG
- Geriatric Depression Scale 2 years post-menopausal or surgically sterile)
- No history of diabetes
- Fasting blood glucose 2X upper limit of normal or aspartate transaminase (AST/SGOT) values > 3X or total bilirubin > 2X.
- Has received acetylcholinesterase inhibitor and/or memantine and/or any other medicine that affects the central nervous system for less than 4 months or has less than 2 months stable therapy on these treatments by baseline visit.
- Current use of specified medications with psychoactive properties that deleteriously affect cognition (e.g., certain antidepressants, anticholinergics, anti-histamines, antipsychotics, sedative hypnotics, anxiolytics)
- Use of investigational agents one month prior to entry and for the duration of the trial
- Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director.
Data sourced from ClinicalTrials.gov (NCT01965756). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.