A Phase 2 interventional study of Metformin and Placebo in Aging, Inflammation and Frailty, sponsored by Mayo Clinic. Terminated at 1 site in United States. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2022-11-17.
Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment
This study will test whether chronic metformin administration will improve longevity of the cell, improves its machinery by reducing aging-related biochemical parameters and thereby improving physical performance, as measured by short physical performance battery test.
Heart disease is the number one cause of death in the United States and disproportionately affects older adults, underscoring the need to examine determinants of survivorship. Recognizing this gap, current guidelines lay emphasis to assess frailty, a key construct prevalent in elderly and known to impact their prognosis.Older persons are commonly frail, manifest hyperglycemia and their health span is truncated by illnesses during which physiological declines together with accumulation of additional deficits results in multimorbidity and functional dependence. High incidence of functional decline and stress hyperglycemia in patients with coronary artery disease (CAD) makes pharmacologic manipulation, an attractive strategy to improve frailty and reduce adverse cardiovascular outcomes. Metformin exerts its effect on health span as a calorie restriction-mimetic through inhibition of mitochondrial complex 1 and activation of activated protein kinase (AMP).This drug is safe and has been shown to prolong life in mammals. Metformin by reducing effects of cellular senescence and improving glycemic control may improve the functioning of older adults.
In CAD, cellular senescence and inflammation affect organ dysfunction through interference with tissue homeostasis and regeneration. The deleterious effect of senescence includes pro-inflammatory senescence-associated secretory phenotype (SASP). Normal biological function through alteration in cellular homeostasis and restoration of glycemic control may be achieved by metformin. The phenotypic manifestations of these changes are incompletely characterized as it is yet unknown whether cell-intrinsic regenerative mechanisms can be translated into clinical improvement in physical performance and whether it's chronic administration is safe in older adults. These major gaps in knowledge hinder utilization of metformin as an agent to promote cellular regeneration and to reduce the impact of cellular senescence.
Targeting frail individuals with high levels of inflammation and SASP factors would necessitate identification of predictors of improvement with metformin in tissue inflammation and function. A clinomics approach implementing simultaneous assessment of clinical impact coupled with serological profiling would provide enhanced understanding of the local and systemic impact mediated by metformin. Through correlation of molecular profiles with phenotypic expression changes, as proposed herein, investigators will enhance understanding of the regenerative impact of metformin and the basis for clinical improvement in the setting of senescence.
1,284 studies on the registry are indexed under Frailty; 452 are open to participants now.
This study's enrollment of 7 is below the median of 81 across 767 interventional studies indexed under Frailty.
Browse Frailty studies →Mayo Clinic is the lead sponsor of 3,269 studies on the registry; 672 are open to participants now.
Of its 452 completed or terminated interventional studies of FDA-regulated products, 321 (71%) have results posted.
Compared within Frailty, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Inflammation. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Prediabetes (one of the following criteria should be met)
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metformin 500mg tablet by mouth, every 6 to 8 hours for one year
Drug: Metformin
Placebo by mouth every 6 to 8 hours for one year
Drug: Placebo
Oral metformin (up to 2gm) will be given in divided doses
Oral Placebo will be given in divided doses
Change in Frailty
Frailty will be measured by the Short Physical Performance Battery (SPPB). The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). Frailty is defined as a score of \<9.
Time frame: Baseline, 12 months
Change in Balance Score Standing With Feet Close Together
This measure is part of the SPPB. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
Time frame: Baseline, 12 months
Change in Balance Score Standing in Semi Tandem Position
This measure is part of the SPPB. The semi tandem position is the heel of one foot place by the big toe of the other foot. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
Time frame: Baseline, 12 months
Change in Balance Score Standing in Full Tandem Position
This measure is part of the SPPB. The full tandem position is with the feet directly in front of each other. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
Time frame: Baseline, 12 months
Change in Gait Speed
This measure is part of the SPPB. Subjects will be asked to walk 8 feet or 2.44 meters at their usual pace. They will be allowed to use a cane or other walking aid if it is their custom. Scores range from 0 = could not do to 4 =\<3.1 seconds.
Time frame: Baseline, 12 months
Change in Score, Standing Test From Chair
This measure is part of the SPPB. Subjects will be asked to try to stand up from a chair 5 times with arms folded across their chest, and will be timed. Scores range from 0 to 4, with 0 = unable to stand without using arms, and 4 = completing 5 stands in \<11.1 seconds.
Time frame: Baseline,12 months
Change in Interleukin 6 (pg/ml)
Serum will be collected to measure the effect of metformin on senescent markers.
Time frame: Baseline, 12 months
Change in Matrix Metalloproteinase (ng/ml)
Serum will be collected to measure the effect of metformin on senescent markers.
Time frame: Baseline, 12 months
Change in Plasminogen Activator Inhibitor
Serum will be collected to measure the effect of metformin on senescent markers.
Time frame: Baseline, 12 months
Change in Monocyte Chemotactic Protein-1
Serum will be collected to measure the effect of metformin on senescent markers.
Time frame: Baseline, 12 months
Change in Activin
Serum will be collected to measure the effect of metformin on senescent markers.
Time frame: Baseline, 12 months
| Milestone | Metformin | Placebo |
|---|---|---|
| Started | 4 | 3 |
| Completed | 2 | 1 |
| Not completed | 2 | 2 |
| Withdrew: Withdrawal by subject | 2 | 2 |
Frailty will be measured by the Short Physical Performance Battery (SPPB). The short physical performance battery (SPPB) is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older people. The scores range from 0 (worst performance) to 12 (best performance). Frailty is defined as a score of \<9.
No measurements were reported for this outcome.
This measure is part of the SPPB. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
No measurements were reported for this outcome.
This measure is part of the SPPB. The semi tandem position is the heel of one foot place by the big toe of the other foot. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
No measurements were reported for this outcome.
This measure is part of the SPPB. The full tandem position is with the feet directly in front of each other. The scores range from 0 (not attempted), to 2 (held for 10 seconds). Ability to stand longer in this position indicates greater balance.
No measurements were reported for this outcome.
This measure is part of the SPPB. Subjects will be asked to walk 8 feet or 2.44 meters at their usual pace. They will be allowed to use a cane or other walking aid if it is their custom. Scores range from 0 = could not do to 4 =\<3.1 seconds.
No measurements were reported for this outcome.
This measure is part of the SPPB. Subjects will be asked to try to stand up from a chair 5 times with arms folded across their chest, and will be timed. Scores range from 0 to 4, with 0 = unable to stand without using arms, and 4 = completing 5 stands in \<11.1 seconds.
No measurements were reported for this outcome.
Serum will be collected to measure the effect of metformin on senescent markers.
No measurements were reported for this outcome.
Serum will be collected to measure the effect of metformin on senescent markers.
No measurements were reported for this outcome.
Serum will be collected to measure the effect of metformin on senescent markers.
No measurements were reported for this outcome.
Serum will be collected to measure the effect of metformin on senescent markers.
No measurements were reported for this outcome.
Serum will be collected to measure the effect of metformin on senescent markers.
No measurements were reported for this outcome.
Collected over Adverse Events were collected from baseline to end of study, approximately 12 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | 0/4 (0%) | 0/4 (0%) | 0/4 (0%) |
| Placebo | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) |
| Age, Continuous(years) | Metformin | Placebo | Total |
|---|---|---|---|
| Mean | 75.75 (64.0 to 86.0) | 77.33 (71.0 to 81.0) | 76.54 (64.0 to 86.0) |
| Sex: Female, Male(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 2 | 2 | 4 |
| Race and Ethnicity Not Collected(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Metformin | Placebo | Total |
|---|---|---|---|
| United States | 4 | 3 | 7 |
Plan to share: No — No plan to do that
This study is terminated, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Metformin