Trial · NCT03733132

Metformin Effect on Brain Function in Insulin Resistant Elderly People

NCT03733132, Phase 2, Completed, Mayo Clinic; results first posted 2024-06-18

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Metformin Effect on Brain Function in Insulin Resistant Elderly People. Trials, record NCT03733132. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03733132

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Metformin Effect on Brain Function in Insulin Resistant Elderly People
NCT number: NCT03733132
Status: Completed
Phases: Phase 2
Enrollment: 40 participants, actual
Lead sponsor: Mayo Clinic
Conditions: Insulin Resistance, Obesity, Obesity, Abdominal
Interventions: Metformin Hydrochloride, Placebo Oral Tablet
First posted: 2018-11-07
Last updated: 2024-06-18
Results first posted: 2024-06-18

Source ClinicalTrials.gov

Registered outcomes5

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in Brain PCr/ATP Ratio as Measured by Phosphorus Magnetic Spectroscopy (31P-MRS) After 10 Months of Metformin Administration	Baseline, 10 months	Multivoxel spectroscopic imaging of the brain will be performed using our dual-tuned single-channel-proton eight-channel-phosphorus head coil. A single 2.5 cm thick slice will be prescribed to encompass the temporal and occipital lobes, and weighted MRSI will be performed using a 16x16 matrix to acquire nominal 2.5 cm3 voxels. Multivoxel phosphorus magnetic resonance spectroscopic imaging data were reconstructed and quantified using jMRUI 6.0. Spectra were preprocessed by (a) truncating the data to 768 points, then 0-filling to 1024 points; (b) apodizing with a 5 Hz Lorenzian; and (c) aligning the data such that the PCr peak was set to 0 Hz. Next, 2 voxels from occipital lobe were selected, extracted, and averaged together into a single free induction decay in order to reduce noise. The outcome measure PCr/ATP ratio is a marker of ATP resynthesis potential and is reported as a change from pre- to post-treatment.
Primary	Change From Baseline in Cognitive Function as Measured by NIH Toolbox After 10 Months of Metformin Administration	Baseline, 10 months	The NIH Toolbox will be utilized to measure cognitive outcomes. The NIH Toolbox-Cognition Battery is composed of 7 tests (\~30 minutes) and our primary outcome measure will be the Total Cognition Composite score comprised from these 7 tests. Results are presented as a fully-adjusted T-score. For a single timepoint, T-scores are expected to have a population mean of 50, standard deviation of 10. For a single timepoint, higher T-scores indicate better cognitive test performance. An increase in T-score over time is considered a better outcome. At the individual level, a T-score \< 40 is considered low test performance. There were no clear clinically relevant thresholds for a change in T-score over 10 months at the start of this study. Comparison of the mean change in T-score over time in the Metformin treatment group to placebo is our analysis of interest
Secondary	Change From Baseline in Brain Structure as Measured by MRI After 10 Months of Metformin Administration	Baseline, 10 months	AA sagittal 3D MPRAGE sequence with 0.7mm isotropic voxels (TR=2400, TE=2.57, TI=1100, FA=8) will be used to acquire high-resolution structural data for volumetric analysis of brain region changes related to metformin. To measure white matter information: 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.
Secondary	Change From Baseline in Muscle Mitochondrial Respiration as Measured by High-resolution Respirometry Following 10 Months of Metformin Administration	Baseline, 10 months	High-resolution respirometry will be used to analyze oxygen consumption in isolated mitochondria from skeletal muscle biopsy samples while simultaneously quantifying reactive oxygen species (ROS) production using amplex red. An increase in mitochondrial respiration is indicative of increased mitochondrial function which is a positive outcome.
Secondary	Change From Baseline in Muscle Mitochondrial ATP Production as Measured by Fluorometry Following 10 Months of Metformin Administration	Baseline, 10 months	Concurrent to mitochondrial respiration, muscle mitochondrial ATP production will be measured using high-sensitivity fluorometry. An increase in mitochondrial ATP production shows increase mitochondrial efficiency which is a positive outcome.

Source ClinicalTrials.gov

Outcomes5

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in Brain PCr/ATP Ratio as Measured by Phosphorus Magnetic Spectroscopy (31P-MRS) After 10 Months of Metformin Administration	Baseline, 10 months	If PCr, γ-ATP, α-ATP, or β-ATP signals were indiscernible from the background noise after processing then those spectra were discarded. Spectra processing was performed by one person, and processing steps were checked for fidelity by a second person. Twelve patients in the placebo group and 15 in the metformin group meet quality control criteria for both the pre- and post-scans.	PCr/ATP ratio	MEAN
PRIMARY	Change From Baseline in Cognitive Function as Measured by NIH Toolbox After 10 Months of Metformin Administration	Baseline, 10 months		t-score	MEAN
SECONDARY	Change From Baseline in Brain Structure as Measured by MRI After 10 Months of Metformin Administration	Baseline, 10 months	One participant in each group was not able to be analyzed due to lack of sufficent scan quality.	mm cubed	MEAN
SECONDARY	Change From Baseline in Muscle Mitochondrial Respiration as Measured by High-resolution Respirometry Following 10 Months of Metformin Administration	Baseline, 10 months	2 participants in each group were unable to be measured for mitochondrial respiration. 2 were due to instrumentation malfunction and 2 were due to inability to collect enough muscle tissue for mitochondrial isolation on one or both study dates.	pmol/sec/mL/mg tissue mass	MEAN
SECONDARY	Change From Baseline in Muscle Mitochondrial ATP Production as Measured by Fluorometry Following 10 Months of Metformin Administration	Baseline, 10 months	5 participants in the placebo group and 6 in the metfomin group were unable to be analyzed. One in each group was due to the inability to collect enough muscle for mitochondrial isolation and the remainder were due to an equipment breakdown (power source - had to be externally source and repaired via service technician) that rendered the equipment unusable for multiple study days.	pmol/sec/ug mitochondrial protein	MEAN

Source ClinicalTrials.gov

Results by group10

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Change From Baseline in Brain PCr/ATP Ratio as Measured by Phosphorus Magnetic Spectroscopy (31P-MRS) After 10 Months of Metformin Administration	Placebo	-0.045	Standard Deviation 0.258	PCr/ATP ratio
Change From Baseline in Brain PCr/ATP Ratio as Measured by Phosphorus Magnetic Spectroscopy (31P-MRS) After 10 Months of Metformin Administration	Metformin	-0.016	Standard Deviation 0.483	PCr/ATP ratio
Change From Baseline in Cognitive Function as Measured by NIH Toolbox After 10 Months of Metformin Administration	Placebo	1.450	Standard Deviation 4.968	t-score
Change From Baseline in Cognitive Function as Measured by NIH Toolbox After 10 Months of Metformin Administration	Metformin	2.900	Standard Deviation 5.543	t-score
Change From Baseline in Brain Structure as Measured by MRI After 10 Months of Metformin Administration	Placebo	-2255.098	Standard Deviation 11757.866	mm cubed
Change From Baseline in Brain Structure as Measured by MRI After 10 Months of Metformin Administration	Metformin	1588.247	Standard Deviation 30282.932	mm cubed
Change From Baseline in Muscle Mitochondrial Respiration as Measured by High-resolution Respirometry Following 10 Months of Metformin Administration	Placebo	-0.106	Standard Deviation 2.752	pmol/sec/mL/mg tissue mass
Change From Baseline in Muscle Mitochondrial Respiration as Measured by High-resolution Respirometry Following 10 Months of Metformin Administration	Metformin	-0.926	Standard Deviation 2.674	pmol/sec/mL/mg tissue mass
Change From Baseline in Muscle Mitochondrial ATP Production as Measured by Fluorometry Following 10 Months of Metformin Administration	Placebo	5.760	Standard Deviation 13.218	pmol/sec/ug mitochondrial protein
Change From Baseline in Muscle Mitochondrial ATP Production as Measured by Fluorometry Following 10 Months of Metformin Administration	Metformin	8.899	Standard Deviation 26.430	pmol/sec/ug mitochondrial protein

Source ClinicalTrials.gov

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Placebo	20
Overall Study	STARTED	Metformin	20
Overall Study	COMPLETED	Placebo	20
Overall Study	COMPLETED	Metformin	20
Overall Study	NOT COMPLETED	Placebo	0
Overall Study	NOT COMPLETED	Metformin	0

Source ClinicalTrials.gov

Adverse events36

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Infections and infestations: Other	Infections and infestations	Placebo	1	20	1
other	Infections and infestations: Other	Infections and infestations	Metformin	0	20	0
other	Pain	General disorders	Placebo	0	20	0
other	Pain	General disorders	Metformin	1	20	1
other	Gastroesophageal reflux disease	Gastrointestinal disorders	Placebo	0	20	0
other	Gastroesophageal reflux disease	Gastrointestinal disorders	Metformin	2	20	2
other	Diarrhea	Gastrointestinal disorders	Placebo	5	20	7
other	Diarrhea	Gastrointestinal disorders	Metformin	7	20	8
other	Social circumstances	Social circumstances	Placebo	0	20	0
other	Social circumstances	Social circumstances	Metformin	1	20	1

1 to 10 of 36Source ClinicalTrials.gov

See all 36 adverse events

Adverse event totals6

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Placebo	0	20
Total, all-cause mortality	Metformin	0	20
Total, other adverse events	Placebo	9	20
Total, other adverse events	Metformin	12	20
Total, serious adverse events	Placebo	1	20
Total, serious adverse events	Metformin	0	20

Source ClinicalTrials.gov

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants1

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

Project	Title	Principal investigators	Organization	Funder	Fiscal years
R21AG060139	Metformin Effect on Brain Function in Insulin Resistant Elderly People	NAIR, K SREEKUMARAN	MAYO CLINIC ROCHESTER	NATIONAL INSTITUTE ON AGING	2018 to 2021

Source NIH RePORTER

Trial comparisons2

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

Comparison	Source
Metformin vs Placebo: deaths from any cause	Trial comparisons
Metformin vs Placebo: serious adverse events	Trial comparisons

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT03733132

GET https://conductscience.org/api/trials/v1/NCT03733132/events?page=2

API reference For AI assistants