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Alzheimer's DiseasePhase 2NCT01965756

Effect of Insulin Sensitizer Metformin on AD Biomarkers

A Phase 2 study testing Metformin in people with Alzheimer's Disease and Vascular Dementia, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 80 years
Conditions the study is for
Alzheimer's Disease, Vascular Dementia, Dementia
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteUnited States
Study dates
Jan 2013to Apr 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • 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
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  • Geriatric Depression Scale < 6
  • Modified Hachinski Ischemic Score < 4
  • No major health issues or diseases expected to interfere with the study
  • Willing to complete all baseline assessments and study procedures
  • Stable on all permitted medications for 8 weeks
  • Not pregnant, lactating or of child-bearing potential (women must be >2 years post-menopausal or surgically sterile)
  • No history of diabetes
  • Fasting blood glucose <126 and/or HgbA1c < 6.4
  • Study partner with frequent contact with patient willing to accompany patient to visits and complete partner study forms
  • No contraindication to metformin

Who cannot join

  • • Any CNS disease other than suspected incipient AD, such as clinical stroke, brain tumor, normal pressure hydrocephalus, brain tumor, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints, Parkinson's disease, frontotemporal dementia, or other neurodegenerative diseases
  • Screening/baseline MRI scans with evidence of infarction or other focal lesions in critical memory structures that may be related to cognitive dysfunction
  • Major active psychiatric illness (e.g., depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year
  • History of alcohol or other substance abuse or dependence within the past two years
  • Pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body or claustrophobia that would preclude MRI scanning
  • History of past or current diabetes, pancreatic or liver disease, renal disease
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  • Any significant systemic illness or unstable medical condition that could affect compliance with study
  • Laboratory abnormalities in B12, TFTs, RPR, Lyme or other common lab parameters that might contribute to cognition or participation in study
  • Coagulopathy or anti-coagulant therapy (such as coumadin) increasing the risk for LP resulting in PT/PTT and INR within 1.5 standard deviations over the upper normal limit.
  • Compromised renal function at screening as determined by creatinine clearance <30mL/min based on Cockcroft-Gault calculation
  • Liver dysfunction at screening as evidenced by alanine transaminase (ALT/SGPT) values > 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylvania, Penn Memory Center

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

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.

Being tested
Metformin, Placebos
Keywords
Alzheimer's Disease, Vascular Dementia, Dementia, Memory Impairment
Medical subject headings
Alzheimer Disease, Dementia, Vascular, Dementia, Memory Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01965756
Study groupRoleWhat they receive
Metformin, Then PlaceboExperimentalParticipants 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.
Receives: Drug: Metformin; Drug: Placebos
Placebo, Then MetforminExperimentalParticipants 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.
Receives: Drug: Metformin; Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Word List Memory Total - ADAS-cog

    Alzheimer's Disease Assessment Scale- Cognitive Sub scale (ADAS-COG). Three trials of 10 words each (30 words total)

    Measured: 16 weeks (total) - measured at baseline, week 8 (crossover), and week 16

Secondary outcomes (1)

  1. Trails-B

    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).

    Measured: 16 weeks- measured at baseline, week 8 (crossover), and week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2013 (estimated)
  2. Study startJan 2013
  3. Primary completion22 Dec 2015
  4. Study completionApr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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 blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01965756
Sponsor's protocol ID
UPenn-AHAF_A2012116
Status last verified
Aug 2017
First submitted
16 Oct 2013
Last updated
21 Sep 2017
Data monitoring committee
Yes

Publications

  • Weinberg MS, He Y, Kivisakk P, Arnold SE, Das S. Effect of Metformin on Plasma and Cerebrospinal Fluid Biomarkers in Non-Diabetic Older Adults with Mild Cognitive Impairment Related to Alzheimer's Disease. J Alzheimers Dis. 2024;99(s2):S355-S365. doi: 10.3233/JAD-230899.

    PubMed 38160357

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin in people with Alzheimer's Disease and Vascular Dementia, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Word List Memory Total - ADAS-cog (time frame: 16 weeks (total) - measured at baseline, week 8 (crossover), and week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01965756, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2017.

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