Metformin Effect on Brain Function in Insulin Resistant Elderly People
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03733132|
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : December 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Insulin Resistance Obesity Obesity, Abdominal||Drug: Metformin Hydrochloride Drug: Placebo Oral Tablet||Phase 2|
Insulin resistance is highly prevalent with advancing age. Metformin is an insulin sensitizer and is currently being extensively investigated for its potential anti-aging effect. However, only very limited information is available on metformin effect on brain, which is a major organ affected by aging. With appropriate experimental design, the investigators are attempting to understand the mechanism of metformin treatment on the physiology of the brain as well as cognitive effects. These studies may uncover relationships that could be favorably manipulated to decrease health risks associated with insulin sensitivity and the effect on the brain.
The study results may lead to a breakthrough in providing either definitive data or sufficiently strong preliminary data regarding metformin's effect on elderly people with insulin resistance, on whether the drug enhances brain mitochondrial function in conjunction with improvement of brain functional network and cognitive function.
The overall hypothesis is that metformin administration to elderly people with insulin resistance enhances brain mitochondrial function in conjunction with improvement of brain function. To test this hypothesis, the investigators will address the following Specific Aims:
- Determine whether 40 weeks of metformin administration in elderly people (> 65 years) with insulin resistance enhances brain mitochondrial ATP production. The investigators will measure brain ATP production by 31P-MRS.
- Determine the effect of 40 weeks of metformin administration in elderly people (> 65 years) with insulin resistance on blood flow and functional network in different areas of brain. As a secondary outcome, the investigators will measure structural changes in white and grey matter areas of brain to determine whether metformin has any effect on brain structure.
- Determine the effect of 40 weeks of metformin administration in elderly people (> 65 years) with insulin resistance on cognitive function. The investigators will utilize the computerized NIH Toolbox to measure cognitive outcomes.
The investigators will also associate outcomes from our specific aims with improvements in whole-body insulin sensitivity and skeletal muscle mitochondrial function.
The investigators propose to complete 40 weeks of study in 40 elderly (> 65 years) participants with fasting glucose between 100 to 140 mg/dl and abdominal girth of >102 cm in men and > 88 cm in women. All participants will be those who are not oral hypoglycemic agents including metformin. In this double-blind placebo trial, the investigators will randomly assign the participants to placebo or metformin in an escalated dose to reach a maximum of 2500 mg per day.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Study will be a double-blind, placebo-controlled, randomized design.|
|Primary Purpose:||Basic Science|
|Official Title:||Metformin Effect on Brain Function in Insulin Resistant Elderly People|
|Actual Study Start Date :||March 15, 2019|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2022|
Placebo Comparator: Placebo
Participants in placebo group will receive Placebo Oral Tablets identical to the metformin tablets for 10 months.
Drug: Placebo Oral Tablet
Placebo treatment of identical tablets to metformin group
Other Name: Placebo
Active Comparator: Metformin
Participants in placebo group will receive an escalating dose of Metformin hydrochloride tablets up to a dose of 2500mg for 10 months.
Drug: Metformin Hydrochloride
Metformin treatment of 2500mg for 10 months in the Metformin group
Other Name: Metformin
- Change from baseline in brain ATP production as measured by phosphorus Magnetic Spectroscopy (31P-MRS) after 10 months of metformin administration [ Time Frame: Baseline, 10 months ]Multivoxel chemical shift imaging (dual-tuned proton (Helmholtz pair)/phosphorus (loop) flex coil will be applied such that the phosphorus loop overlies the right DLPFC, WIP 1071, axial 1.5 cm slice prescribed to encompass the right dorsolateral prefrontal cortex, 12x12 matrix reconstructed to 16x16 matrix, 1.5 cm nominal isotropic voxels, TR=1500) will be used to acquire phosphorus metabolite information from the right DLPFC
- Change from baseline in brain structure as measured by functional MRI (fMRI) after 10 months of metformin administration [ Time Frame: Baseline, 10 months ]An axial 2D symmetric multi-slice (SMS) diffusion tensor imaging (DTI) sequence with 60 diffusion directions, 5 B0 acquisitions and 2mm isotropic voxels (TR=3000, TE=73, FA=90, ETL 43, both A-P and P-A phase encoding for B0 images) will be used to acquire white matter integrity data related to metformin.
- Change from baseline in cognitive function as measured by NIH Toolbox Cognitive Battery after 10 months of metformin administration [ Time Frame: Baseline, 10 months ]
- Change from baseline in muscle mitochondrial respiration as measured by oximetry. [ Time Frame: Baseline, 10 months ]Oxygen flux in isolated muscle mitochondria will be measured using a titrated substrate protocol on an Oroboros oximetry instrument.
- Change from baseline in brain blood flow as measured by functional MRI after 10 months of metformin administration [ Time Frame: Baseline, 10 months ]To measure global brain blood flow information: An axial 3D pseudo-continuous arterial spin labelling (pCASL) sequence (WIP 818) with 4mm isotropic voxels (TI1=1800, TI2=3600, iPat ≤ 2) will be used to acquire quantitative blood flow measurements (flow in ml/100g/min) throughout the brain.
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): NCT03733132
|Contact: Susan Sawinski||507-284-8359||Sawinski.Susan@mayo.edu|
|United States, Minnesota|
|Mayo Clinic in Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||K Sreekumaran Nair, M.D., Ph.D.||Mayo Clinic|