A Phase 2 interventional study of Losartan and Placebo in Sarcopenia, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 70 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-06-12.
Sponsored by Johns Hopkins University · Phase 2, Interventional, and Prevention
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.
The loss of independence in older adults is among the most costly and disturbing events in the life span. This loss is often influenced by multiple etiologies, including medical and neurological conditions, cognitive decline, non-supportive social/environmental settings and frailty. Frailty is a syndrome of multi-systemic, age-related decline characterized by weakness, weight loss, fatigue, low levels of activity, and slowness. Frail older adults have a higher risk for adverse outcomes including hospitalization, disability, and mortality.
Recently, Johns Hopkins University Older Americans Independence Center (JHU OAIC) investigators Burks and Cohn found that blocking angiotensin type 1 receptors with losartan, an angiotensin-receptor blocker (ARB) in older mice markedly accelerated injured skeletal muscle healing and decreased vulnerability to disuse atrophy and strength decline. These findings provide potent rationale for testing the hypothesis that losartan attenuates strength decline and other-frailty related measures in older adults.
To prepare to test this hypothesis, a phase 2 randomized, placebo controlled pilot clinical trial of losartan in pre-frail adults over age 70 is proposed that aims to assess safety and tolerability, estimate dosing range, and estimate treatment effects using inter- and intra-subject variability of potential outcome measures. Losartan is a medication that is commonly utilized in older adults for the treatment of hypertension and is generally well tolerated in that condition and in other cardiovascular conditions.
The study will take place over 24 weeks in the Clinical Research Unit (CRU) on the Hopkins Bayview Medical Campus, where 24 pre-frail subjects will be recruited from the OAIC frailty registry. Successful completion of this study will provide the safety, dosing, and outcome measure data necessary to design the pivotal study needed to determine if longer term treatment with losartan can significantly improve frailty and related skeletal muscle phenotypes.
Interventions, such as losartan, that can prevent the decline seen in frailty have the potential to improve function and help older adults maintain their independence. This is of the utmost importance in maintaining good quality-of-life for older adults.
1,208 studies on the registry are indexed under Sarcopenia; 402 are open to participants now.
This study's enrollment of 37 is below the median of 60 across 775 interventional studies indexed under Sarcopenia.
Browse Sarcopenia studies →Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.
Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
For those subjects randomized to placebo, they will receive a placebo to take for 24 weeks total.
Drug: Placebo
Losartan will be given in increasing doses to those in the losartan arm.
Placebo will be given to those in placebo arm
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Week 24
Number of Participants Experiencing Any Amount of Decrease in Frailty
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 8 (i.e., improvement in frailty status)
Time frame: from baseline to 8 weeks
Number of Participants Experiencing Any Amount of Decrease in Frailty
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 16 (i.e., improvement in frailty status)
Time frame: from baseline to 16 weeks
Number of Participants Experiencing Any Amount of Decrease in Frailty
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 24 (i.e., improvement in frailty status)
Time frame: from baseline to 24 weeks
| Milestone | Losartan | Placebo |
|---|---|---|
| Started | 18 | 19 |
| Completed | 10 | 15 |
| Not completed | 8 | 4 |
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.
| Newton | Losartan | Placebo |
|---|---|---|
| Change From Baseline in Isokinetic Strength | -4.90 ± 11.76 | -4.73 ± 8.81 |
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.
| Newton | Losartan | Placebo |
|---|---|---|
| Change From Baseline in Isokinetic Strength | -7.40 ± 9.56 | -4.27 ± 11.54 |
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.
| Newton | Losartan | Placebo |
|---|---|---|
| Change From Baseline in Isokinetic Strength | -9.20 ± 8.94 | -7.00 ± 10.24 |
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.
| percentage of work | Losartan | Placebo |
|---|---|---|
| Fatiguability | 14.29 ± 9.65 | 7.87 ± 15.31 |
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.
| percentage of work | Losartan | Placebo |
|---|---|---|
| Fatiguability | 16.51 ± 18.92 | 8.77 ± 12.15 |
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.
| percentage of work | Losartan | Placebo |
|---|---|---|
| Fatiguability | 17.07 ± 15.34 | 9.05 ± 14.15 |
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 8 (i.e., improvement in frailty status)
| Participants | Losartan | Placebo |
|---|---|---|
| Number of Participants Experiencing Any Amount of Decrease in Frailty | 3 | 6 |
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 16 (i.e., improvement in frailty status)
| Participants | Losartan | Placebo |
|---|---|---|
| Number of Participants Experiencing Any Amount of Decrease in Frailty | 3 | 5 |
Number of participants experiencing any amount of decrease in frailty score from baseline to Week 24 (i.e., improvement in frailty status)
| Participants | Losartan | Placebo |
|---|---|---|
| Number of Participants Experiencing Any Amount of Decrease in Frailty | 3 | 5 |
Collected over 24 weeks. Non-serious events are listed at a 4% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Losartan | 1/18 (5.6%) | 1/18 (5.6%) | 4/18 (22.2%) |
| Placebo | 0/19 (0%) | 0/19 (0%) | 0/19 (0%) |
| Event | Losartan | Placebo |
|---|---|---|
| Myocardial InfarctionCardiac disorders | 1/18 | 0/19 |
| Event | Losartan | Placebo |
|---|---|---|
| FatigueGeneral disorders | 1/18 | 0/19 |
| HypertensionVascular disorders | 1/18 | 0/19 |
| CreatinineMetabolism and nutrition disorders | 1/18 | 0/19 |
| HyperkalemiaMetabolism and nutrition disorders | 1/18 | 0/19 |
| Age, Categorical(Participants) | Losartan | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 18 | 19 | 37 |
| Sex: Female, Male(Participants) | Losartan | Placebo | Total |
|---|---|---|---|
| Female | 8 | 7 | 15 |
| Male | 10 | 12 | 22 |
| Race (NIH/OMB)(Participants) | Losartan | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 1 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 3 | 6 |
| White | 14 | 15 | 29 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
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