Pilot Study on Evaluating the Geroprotective Effect of Metformin

Aging Clinical Trial

— AGE-M  

Official title:

A Phase II Exploratory Clinical Study Investigating the Geroprotective Effect of Metformin in Middle-aged and Elderly People

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06459310
• Other study ID #: lijingxw
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2024
• Est. completion date: July 31, 2028

Study information

• Verified date: January 2024
• Source: Xuanwu Hospital, Beijing
• Contact: Lingling Geng
• Phone: 18510932169
• Email: gengll[@]xwhosp.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this research is to assess the efficacy of oral metformin in mitigating the aging process in middle-aged and elderly males, to pinpoint sensitive indicators of human senescence, and to offer innovative frameworks and scientific insights for pharmaceutical interventions in aging.

Description:

Subjects in both the metformin hydrochloride extended-release tablets treatment group and the placebo group received two tablets (500 mg each) once daily after dinner, continuing for a one-year period of drug intervention.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: July 31, 2028
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male

2. Age 55-65; 18-28;

3. Able to understand and execute instructions;

4. After reading the consent form, be able to answer questions about the study and demonstrate understanding of the protocol;

5. Be able to participate in regular follow-up visits.

Exclusion Criteria

1. Severe chronic or acute disease: cancer, clinically significant congestive heart failure, chronic obstructive pulmonary disease (COPD), previous or new-onset diabetes, inflammatory state, serum creatinine >1.5 mg/dl , active liver disease, History of metabolic acidosis, poorly controlled hypertension, epilepsy, recent (within 3 months) cardiovascular events (MI, PTCA, CABG, stroke), severe renal insufficiency, inflammatory bowel disease, persistent glucocorticoids Treatment; neurological diseases such as dementia, AD, PD, etc.; infectious diseases such as HIV, hepatitis, tuberculosis, etc.; severe autoimmune diseases;

2. BMI<18.5 or BMI>30;

3. Persistent alcohol or drug abuse;

4. Treatment with drugs known to affect glucose metabolism (other diabetes drugs, systemic glucocorticoids, niacin);

5. Hypersensitivity to metformin or any component of the preparation;

6. Have taken metformin, low-dose aspirin, acarbose, vitamin C in the recent (3 months);

7. Unable to provide informed consent;

8. Other circumstances in which the researcher believes that the physical factors of the participants may adversely affect the research process or results.

Related Conditions & MeSH terms

• Aging
• Metformin

Intervention

Drug:
• Metformin Hydrochloride tablet
Extended release oral tablets, 1000 mg/day, single dose
• Placebo
Oral tablets, 1000 mg/day, single dose

Locations

Country	Name	City	State
China	Xuanwu Hospital Capital Medical University	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing	Beijing Institute of Genomics, Chinese Academy of Sciences, Institute of Zoology, Chinese Academy of Sciences, Merck Serono Co., Ltd., China

Country where clinical trial is conducted

China, 

References & Publications (14)

Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cocheme HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell. 2013 Mar 28;153(1):228-39. doi: 10.1016/j.cell.2013.02.035. — View Citation

Chai M, Jiang M, Vergnes L, Fu X, de Barros SC, Doan NB, Huang W, Chu J, Jiao J, Herschman H, Crooks GM, Reue K, Huang J. Stimulation of Hair Growth by Small Molecules that Activate Autophagy. Cell Rep. 2019 Jun 18;27(12):3413-3421.e3. doi: 10.1016/j.celrep.2019.05.070. — View Citation

Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B. Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66. doi: 10.1016/j.cmet.2014.09.018. Epub 2014 Oct 30. — View Citation

Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med. 1997 Dec;103(6):491-7. doi: 10.1016/s0002-9343(97)00254-4. — View Citation

Gronich N, Rennert G. Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol. 2013 Nov;10(11):625-42. doi: 10.1038/nrclinonc.2013.169. Epub 2013 Oct 1. — View Citation

Kodali M, Attaluri S, Madhu LN, Shuai B, Upadhya R, Gonzalez JJ, Rao X, Shetty AK. Metformin treatment in late middle age improves cognitive function with alleviation of microglial activation and enhancement of autophagy in the hippocampus. Aging Cell. 2021 Feb;20(2):e13277. doi: 10.1111/acel.13277. Epub 2021 Jan 14. — View Citation

Kulkarni AS, Gubbi S, Barzilai N. Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. 2020 Jul 7;32(1):15-30. doi: 10.1016/j.cmet.2020.04.001. Epub 2020 Apr 24. — View Citation

Li C, Mu N, Gu C, Liu M, Yang Z, Yin Y, Chen M, Wang Y, Han Y, Yu L, Ma H. Metformin mediates cardioprotection against aging-induced ischemic necroptosis. Aging Cell. 2020 Feb;19(2):e13096. doi: 10.1111/acel.13096. Epub 2020 Jan 14. — View Citation

Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Epub 2023 Jan 3. — View Citation

Ma T, Tian X, Zhang B, Li M, Wang Y, Yang C, Wu J, Wei X, Qu Q, Yu Y, Long S, Feng JW, Li C, Zhang C, Xie C, Wu Y, Xu Z, Chen J, Yu Y, Huang X, He Y, Yao L, Zhang L, Zhu M, Wang W, Wang ZC, Zhang M, Bao Y, Jia W, Lin SY, Ye Z, Piao HL, Deng X, Zhang CS, Lin SC. Low-dose metformin targets the lysosomal AMPK pathway through PEN2. Nature. 2022 Mar;603(7899):159-165. doi: 10.1038/s41586-022-04431-8. Epub 2022 Feb 23. — View Citation

Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013;4:2192. doi: 10.1038/ncomms3192. — View Citation

Neumann B, Baror R, Zhao C, Segel M, Dietmann S, Rawji KS, Foerster S, McClain CR, Chalut K, van Wijngaarden P, Franklin RJM. Metformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells. Cell Stem Cell. 2019 Oct 3;25(4):473-485.e8. doi: 10.1016/j.stem.2019.08.015. — View Citation

TODAY Study Group; Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, Cuttler L, Nathan DM, Tollefsen S, Wilfley D, Kaufman F. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012 Jun 14;366(24):2247-56. doi: 10.1056/NEJMoa1109333. Epub 2012 Apr 29. — View Citation

Williams-Herman D, Johnson J, Teng R, Golm G, Kaufman KD, Goldstein BJ, Amatruda JM. Efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy over 2 years in patients with type 2 diabetes. Diabetes Obes Metab. 2010 May;12(5):442-51. doi: 10.1111/j.1463-1326.2010.01204.x. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite the efficacy of metformin in intervening aging	Metformin delay aging related sensitive indicators (2), such as SA*, ancient virus *.; Metformin inhibits markers of inflammation in the body (4), such as C1 protein *, CRP, CXCL9, TNFa.; Metformin improved immune cell-related indicators (10*), such as T1/T2/L gene expression.; Metformin improves metabolism-related indexes (4), such as metabolic secretion factors APOX1* and APOX2*.; Age-related indicators have been published (5), such as telomere length, DNA methylation age, hormone levels, etc.	Baseline - 12 month
Secondary	Composite Through clinical physical examination data, behavioral indicators and multilevel omics data, to discover new sensitive biomarkers for evaluating aging.	Aging atlas-R, PBMC RNA profiling, >5% DEGs.; Aging atlas-P, proteomic profiling, >5% DEPs.; Aging atlas-M, metabolic profiling, >5% metabolites.; Aging atlas-B, metagenomic profiling, >5% microbiotas.; Reduce human biological age complex parameters.	Baseline - 12 month