AgingPhase 2NCT03451006
Effect of Metformin on Frailty in 12 Subjects
A Phase 2 study testing Metformin in people with Aging and Inflammation, run by Mayo Clinic at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Aging, Inflammation, Frailty
- 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
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2018to 16 Dec 2021
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 60 years
- Stable CAD
- Prediabetes (one of the following criteria should be met)
- Fasting plasma glucose: 100-126 mg/dL
- HbA1C: 5.7-6.4
- Frailty (Short Physical Performance Battery: Score <9)
- Able to return for follow-up
- Written informed consent
Who cannot join
- Pre-existing or new-onset diabetes
- Any active malignancy, hematological disorder, post organ transplant, immunocompromised
- Cancer requiring treatment in the past 3 years (other than non-melanoma skin cancer)
- Dementia [mini mental state examination (MMSE <20)]
- Disability (need for assistance in >2 of any six activities on Katz activities of daily living (ADL)46
- Prior stroke with disability
Show all 14Show fewer
- Acute coronary syndrome <3months or participating in cardiac rehabilitation
- Severe Parkinson's
- Hepatic insufficiency and/or chronic liver disease (cirrhosis)
- Chronic kidney disease (GFR < 45 mL/min)
- Taking metformin for any indication
- Acute alcohol intoxication
- Known hypersensitivity to metformin hydrochloride
- Acute/chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: (MATE) Metformin and Aging Trial in the Elderly: A Pilot and Feasibility Study
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.
Read the detailed description
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.
- Conditions
- Aging, Inflammation, Frailty
- Being tested
- Metformin, Placebo
- Medical subject headings
- Inflammation, Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Oral metformin (up to 2gm) will be given in divided doses
PlaceboDrug
Oral Placebo will be given in divided doses
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin 500mg tablet by mouth, every 6 to 8 hours for one year Receives: Drug: Metformin |
| Placebo | Active comparator | Placebo by mouth every 6 to 8 hours for one year Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline,12 months
Secondary outcomes (5)
Change in Interleukin 6 (pg/ml)
Serum will be collected to measure the effect of metformin on senescent markers.
Measured: Baseline, 12 months
Change in Matrix Metalloproteinase (ng/ml)
Serum will be collected to measure the effect of metformin on senescent markers.
Measured: Baseline, 12 months
Change in Plasminogen Activator Inhibitor
Serum will be collected to measure the effect of metformin on senescent markers.
Measured: Baseline, 12 months
Change in Monocyte Chemotactic Protein-1
Serum will be collected to measure the effect of metformin on senescent markers.
Measured: Baseline, 12 months
Change in Activin
Serum will be collected to measure the effect of metformin on senescent markers.
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start24 May 2018
- Primary completion16 Dec 2021
- Study completion16 Dec 2021
Why it stopped: difficult recruitment and not achieved
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Model description
- Arms Assigned interventions Placebo Comparator: Metformin Chronic metformin administration through augmentation of cellular regeneration and reduction of senescence will improve frailty and physical functioning as studied by the short physical performance battery (SPPB) test. Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score \<9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months. Placebo comparator: Placebo Placebo will be compared to chronic metformin administration Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score \<9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mandeep Singh, Mayo Clinic
- Investigators
- Mandeep Singh, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03451006
- Sponsor's protocol ID
- 17-003088
- Status last verified
- Oct 2022
- First submitted
- 30 Jan 2018
- Last updated
- 17 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to do that
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- (MATE) Metformin and Aging Trial in the Elderly: A Pilot and Feasibility Study
- ClinicalTrials.gov ID
- NCT03451006
- Acronym / sponsor ID
- 17-003088
- Conditions
- Aging, Inflammation, Frailty
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: difficult recruitment and not achieved
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 24 May 2018 (actual)
- Primary completion
- 16 Dec 2021 (actual)
- Study completion
- 16 Dec 2021 (actual)
- First posted
- 1 Mar 2018 (actual)
- Results
- Posted 17 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Arms Assigned interventions Placebo Comparator: Metformin Chronic metformin administration through augmentation of cellular regeneration and reduction of senescence will improve frailty and physical functioning as studied by the short physical performance battery (SPPB) test. Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score <9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months. Placebo comparator: Placebo Placebo will be compared to chronic metformin administration Drug: Metformin versus placebo This will be a pilot, feasibility study. Twelve subjects ≥60 years with stable CAD and prediabetes, who score <9 on SPPB test will be randomized to receive up to 2gm of oral metformin or placebo for 12 months.
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminMetformin 500mg tablet by mouth, every 6 to 8 hours for one year |
| Placebo | Active comparator | Drug: PlaceboPlacebo by mouth every 6 to 8 hours for one year |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 60 years
- Stable CAD
- Prediabetes (one of the following criteria should be met)
- Frailty (Short Physical Performance Battery: Score <9)
- Able to return for follow-up
Key exclusion criteria (14 listed)
- Pre-existing or new-onset diabetes
- Any active malignancy, hematological disorder, post organ transplant, immunocompromised
- Cancer requiring treatment in the past 3 years (other than non-melanoma skin cancer)
- Dementia [mini mental state examination (MMSE <20)]
- Disability (need for assistance in >2 of any six activities on Katz activities of daily living (ADL)46
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminOral metformin (up to 2gm) will be given in divided doses | Drug | Metformin |
| PlaceboOral Placebo will be given in divided doses | Drug | Placebo |
Primary outcome
Change in Frailty
Time frame: Baseline, 12 months
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.
Change in Balance Score Standing With Feet Close Together
Time frame: Baseline, 12 months
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.
Change in Balance Score Standing in Semi Tandem Position
Time frame: Baseline, 12 months
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.
Change in Balance Score Standing in Full Tandem Position
Time frame: Baseline, 12 months
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.
Change in Gait Speed
Time frame: Baseline, 12 months
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.
Change in Score, Standing Test From Chair
Time frame: Baseline,12 months
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.
5 secondary outcomes
Change in Interleukin 6 (pg/ml)
Time frame: Baseline, 12 months
Change in Matrix Metalloproteinase (ng/ml)
Time frame: Baseline, 12 months
Change in Plasminogen Activator Inhibitor
Time frame: Baseline, 12 months
Change in Monocyte Chemotactic Protein-1
Time frame: Baseline, 12 months
Change in Activin
Time frame: Baseline, 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No. No plan to do that
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mandeep Singh principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Aging and Inflammation, run by Mayo Clinic 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 8 inclusion and 14 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: stopped early, as of the sponsor's last update on 17 Nov 2022. 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 17 Nov 2022). 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?
Change in Frailty (time frame: Baseline, 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Nov 2022.