A Study of Muscle Strength Maintenance in Older Adults

NCT01989793 | Completed Phase 2 Results DMC

• 2 other identifiers: NA_00078435P30AG021334
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being done to see whether losartan can prevent the decrease in strength associated with aging. Muscle loss is associated with aging and has multiple symptoms such as weakness, slowness, and fatigue (tiredness). Older adults with muscle weakness have a higher risk of falls and disability. In addition, the loss of independence for older adults can lead to a poorer quality of life. Recently, it was discovered that losartan, a medication commonly used to treat high blood pressure, had slowed the strength decline seen in older mice. In addition, it allowed injured mice skeletal muscle to heal faster. Therefore, we would like to see if losartan can do the same for older adults. Losartan is approved by the Food and Drug Administration (FDA) for the treatment of high blood pressure, heart failure, and to protect the kidneys in diabetic patients. Losartan is not FDA-approved to prevent the decrease in strength associated with aging. In this study, participants age 70 and older will be asked to take losartan or a placebo to see if losartan can help prevent loss of muscle strength. A placebo is a substance that looks like the study drug but that contains no active ingredients.

Conditions

Sarcopenia

Keywords

sarcopenia; frailty; losartan

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Isokinetic Strength

  Isokinetic Strength was measured by knee extension exercises where bilateral knee concentric strength was measured using a Biodex System 3 dynamometer set at an angular velocity of 30deg/sec through a joint arc from 90 degrees to 30 degrees (0 degrees- full extension). The change in strength between baseline and week 8 (i.e., baseline minus week 8) was the outcome of the analysis. A negative number indicates that there was a decrease in isokinetic strength from week 0 to week 8.

  Baseline to Week 8

• Change From Baseline in Isokinetic Strength

  Isokinetic Strength was measured by knee extension exercises where bilateral knee concentric strength was measured using a Biodex System 3 dynamometer set at an angular velocity of 30deg/sec through a joint arc from 90 degrees to 30 degrees (0 degrees- full extension). The change in strength between baseline and week 16 (i.e., baseline minus week 16) was the outcome of the analysis. A negative number indicates decrease in strength from week 0 to week 16.

  Baseline to Week 16

• Change From Baseline in Isokinetic Strength

  Isokinetic Strength was measured by knee extension exercises where bilateral knee concentric strength was measured using a Biodex System 3 dynamometer set at an angular velocity of 30deg/sec through a joint arc from 90 degrees to 30 degrees (0 degrees- full extension). The change in strength between baseline and week 24 (i.e., baseline minus week 24) was the outcome of the analysis. A negative number indicates a decrease in strength from week 0 to week 24.

  Baseline to Week 24

• Fatiguability

  Fatiguability was tested using bilateral knee extension with an external load equal to 40% of the maximal voluntary contraction force. Fatiguability was defined as the ratio (expressed as a percentage) of the total work in the last 3 of the 10 repetitions to the total work in the first 3 of the 10 repetitions, where the total work for n repetitions is defined as the sum of peak torque (FT-LBS) over n repetitions (i.e., last three reps/first three reps). The maximum of the two sides was used in the analysis.

  Week 8

• Fatiguability

  Fatiguability was tested using bilateral knee extension with an external load equal to 40% of the maximal voluntary contraction force. Fatiguability was defined as the ratio (expressed as a percentage) of the total work in the last 3 of the 10 repetitions to that of the first 3 of the 10 repetitions, where the total work for n repetitions is defined as the sum of peak torque (FT-LBS) over n repetitions (i.e., last three reps/first three reps). The maximum of the two sides was used in the analysis.

  Week 16

• Fatiguability

  Fatiguability was tested using bilateral knee extension with an external load equal to 40% of the maximal voluntary contraction force. Fatiguability was defined as the ratio (expressed as a percentage) of the total work in the last 3 of the 10 repetitions to that of the first 3 of the 10 repetitions, where the total work for n repetitions is defined as the sum of peak torque (FT-LBS) over n repetitions (i.e., last three reps/first three reps). The maximum of the two sides was used in the analysis.

  Week 24

Secondary Outcomes (3)

• Number of Participants Experiencing Any Amount of Decrease in Frailty

  from baseline to 8 weeks

• Number of Participants Experiencing Any Amount of Decrease in Frailty

  from baseline to 16 weeks

• Number of Participants Experiencing Any Amount of Decrease in Frailty

  from baseline to 24 weeks

Study Arms (2)

Losartan

ACTIVE COMPARATOR

For those subjects randomized to the losartan group, they will receive losartan 25mg by mouth daily for 8 weeks, then increase to 50mg by mouth daily for another 8 weeks, then increase to 100mg by mouth daily for a final 8 weeks.

Drug: Losartan

Placebo

PLACEBO COMPARATOR

For those subjects randomized to placebo, they will receive a placebo to take for 24 weeks total.

Drug: Placebo

Interventions

Losartan DRUG

Losartan will be given in increasing doses to those in the losartan arm.

Losartan

Placebo DRUG

Placebo will be given to those in placebo arm

Placebo

Eligibility Criteria

• Age: 70 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 70 and over
• Pre-frail as determined by frailty criteria

You may not qualify if:

• Under age 70
• Robust or frail by frailty criteria
• Have other indications for use of any angiotensin-receptor blockers (ARB) such as myocardial infarction in past year, history of congestive heart failure, uncontrolled hypertension
• Current use of ARBs or angiotensin-converting enzyme (ACE) inhibitors
• Prior allergic reaction to or hyperkalemia with losartan or any ARB
• Chronic renal failure with a glomerular filtration rate of \< 30
• Current daily use of non-steroidal anti-inflammatory agents
• Current use of steroids
• Lower extremity disability that would prevent muscle strength testing
• Echocardiogram-diagnosed cardiac failure as evidenced by left ventricular ejection fraction less than 50%
• Cognitive impairment with a Mini-Mental State Examination \< 24

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Johns Hopkins Bayview Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• Burks TN, Andres-Mateos E, Marx R, Mejias R, Van Erp C, Simmers JL, Walston JD, Ward CW, Cohn RD. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37. doi: 10.1126/scitranslmed.3002227.

  PMID: 21562229 BACKGROUND

• Abadir PM, Foster DB, Crow M, Cooke CA, Rucker JJ, Jain A, Smith BJ, Burks TN, Cohn RD, Fedarko NS, Carey RM, O'Rourke B, Walston JD. Identification and characterization of a functional mitochondrial angiotensin system. Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14849-54. doi: 10.1073/pnas.1101507108. Epub 2011 Aug 18.

  PMID: 21852574 BACKGROUND

• Lee JL, Zhang C, Westbrook R, Gabrawy MM, Nidadavolu L, Yang H, Marx R, Wu Y, Anders NM, Ma L, Bichara MD, Kwak MJ, Buta B, Khadeer M, Yenokyan G, Tian J, Xue QL, Siragy HM, Carey RM, de Cabo R, Ferrucci L, Moaddel R, Rudek MA, Le A, Walston JD, Abadir PM. Serum Concentrations of Losartan Metabolites Correlate With Improved Physical Function in a Pilot Study of Prefrail Older Adults. J Gerontol A Biol Sci Med Sci. 2022 Dec 29;77(12):2356-2366. doi: 10.1093/gerona/glac102.

  PMID: 35511890 DERIVED

Related Links

• Johns Hopkins Trials listing

MeSH Terms

Conditions

Sarcopenia; Frailty

Interventions

Losartan

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Dr. Jeremy D. Walston, M.D. , Raymond and Anna Lublin Professor of Geriatric Medicine
• Organization: Johns Hopkins University

jwalston@jhmi.edu

410-550-1003

Study Officials

• Jeremy Walston, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 21, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 12, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-05

Locations

US (1)