- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04021706
Effect of a Ghrelin Receptor Agonist on Muscle and Bone
February 27, 2024 updated by: Bess Dawson-Hughes, Tufts University
Adults with low muscle mass also usually have low bone mass, making them vulnerable to falls, fractures and other injuries.
This project will determine the effectiveness of treatment with a ghrelin receptor agonist in improving short term indicators of muscle and bone health in adults with low bone and muscle mass.
The results of this trial will inform the design of a larger, definitive randomized trial designed to establish efficacy.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Adults with both osteopenia and sarcopenia (osteosarcopenia) have greater risk of falls and fractures than those with osteopenia or sarcopenia alone.
Drugs are available to reduce fracture risk but currently exercise is the only effective strategy to combat muscle loss.
Unfortunately, the majority of adults who start a self-monitored exercise program drop out after 6 months and other options are needed.
Ghrelin receptor agonists have been under development to treat anorexia and weight loss in patients with cancer cachexia.
The agonist anamorelin has significantly increased weight and lean tissue mass in these patients.
Anamorelin mimics the hormone ghrelin which not only increases appetite, but also acts on the pituitary to increase pulsatile growth hormone (GH) secretion.
Pulsatile GH stimulates the production of insulin-like growth factor 1 which is anabolic to both muscle and bone.
GH levels decline with age and this is thought to contribute to the age-related muscle and bone losses in adults.
The central hypothesis is that anamorelin will increase muscle mass, improve muscle function, and increase bone formation in adults with osteosarcopenia.
To test this hypothesis, the investigators will conduct a randomized, double-blind, 2-armed, parallel-group intervention trial in 32 osteosarcopenic men and postmenopausal women age 50 and older.
Participants will be randomized to anamorelin (100 mg per day) or placebo and treated for 12 months.
The primary endpoint is change from baseline in muscle mass by D3-creatine dilution.
Secondary endpoints are:appendicular lean tissue mass/ht2 (ALM/ht2) measured by dual-energy x-ray absorptiometry (DXA); the bone formation biomarker, amino-terminal propeptide (P1NP), total body lean mass by DXA.
Exploratory outcomes are changes in isokinetic leg strength, grip strength, and muscle performance (Health ABC-Physical Performance Battery (HABC-PPB), serum IGF-1 and C-telopeptide (CTX), and spine and hip bone mineral density (BMD).
The proposed treatment supplies the anabolic stimulus to build both muscle and bone.
Anamorelin has not been tested in adults with osteosarcopenia.
The investigators propose to evaluate this treatment in osteosarcopenic adults who are most in need of treatment and who are also most likely to benefit.
Data obtained from this pilot study are critical to determine the feasibility and guide the design of a definitive trial to evaluate this ghrelin receptor agonist as potential therapy to mitigate the dual hazards of osteopenia and sarcopenia.
Study Type
Interventional
Enrollment (Actual)
32
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02111
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Ability to sign informed consent form
Community dwelling individuals aged 50 years and older
- Men (who are sterile or agree to use contraception throughout the study)
- Postmenopausal women (no menses for 5 years; early postmenopausal women are ineligible because their bone turnover rate is changing rapidly)
- Sarcopenia defined as maximum grip strength <35.5 kg (men) and <20 kg (women) in either hand (excluding hands with severe pain or recent surgery) and/or gait speed <0.8 m/sec
- Osteopenia defined as spine (at L1, L2, L3, or L4) or total hip or femoral neck BMD T-score between -1.0 and -2.5
- Mini-mental state examination (MMSE) score >21
Exclusion Criteria:
- BMI > 30 kg/m2 (obese are ineligible because anamorelin may cause weight gain)
- Osteoporosis of the spine or hip by DXA scan (specifically, T-score ≤ -2.5 at two lumbar vertebrae or at the total hip or femoral neck, as recommended by the International Society for Clinical Densitometry [ISCD])
- Current participation in a fitness program or weight loss program
- Advanced knee osteoarthritis (OA) or other conditions preventing strength or function testing
- Lower extremity fracture in the last year
- Diabetics taking insulin or sulfonylureas and subjects with a fasting blood sugar on screening >150 mg/dl
- Inadequate hepatic function defined as AST and ALT levels > 2 x upper limit of normal at screening (>74 and >68 MU/ml, respectively)
- Untreated thyroid or parathyroid disease
- Significant immune disorder
- eGFR<30 ml/min
- Any clinically meaningful electrocardiogram (ECG) abnormality on screening or baseline
- Crohn's disease
- Active malignancy or cancer therapy in the last year
- Non-English speaking subjects (the investigators can't be confident that non-English speaking subjects could accurately complete the diet assessments which are critical to the integrity of the study)
- Allergy to components of the study interventions
- Other condition or abnormality in screening labs at discretion of the study physician (the PI)
Medications:
- Osteoporosis treatment - teriparatide, abaloparatide, raloxifene, denosumab, or romosozumab in the last 12 mo or a bisphosphonate in the last 2 years
- Tamoxifen in the last 6 mo
- Cancer treatment in the last 3 years (except basal cell skin cancer)
- strong CYP3A4 inhibitors within the previous two weeks (ketoconazole, clarithromycin, itraconazole, nefazodone, telithromycin)since anamorelin is mainly metabolized by CYP3A4
- Use of drugs that may prolong the PR or QRS interval durations, such as any of the Class I/Sodium (Na+) Channel blocking antiarrhythmic medications (e.g. flecainide, procainamide, propafenone, quinidine)
- Drugs with high affinity to alpha-acid glycoprotein (AAG) and therefore with potential to displace anamorelin from binding (e.g., carvedilol, chlorpromazine)
- Inhibitors of P-glycoprotein (e.g., verapamil, quinidine), and inhibitors of OATP1B3 (e.g., cyclosporine, rifampicin)
- CYP3A4 inducers (e.g., rifampin)
- Oral or IV glucocorticoids (>10 days in the last 3 mo)
- Gonadal hormones (vaginal estrogen okay)
- Drugs to promote weight loss or gain
- TNF-α inhibitors (e.g., adalimumab, adalimumab-atto, certolizumab pegol, etanercept, etanercept-szzs, golimumab, infliximab)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: anamorelin
one 100 mg tablet daily, taken one hour before breakfast
|
Ghrelin receptor agonist
|
Placebo Comparator: microcrystaline cellulose
one identical appearing tablet daily, taken one hour before breakfast
|
placebo is a inert substance
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Body Muscle Mass
Time Frame: baseline and 12 months
|
to be assessed by D3-creatine dilution
|
baseline and 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Procollagen 1 Intact N-terminal (P1NP)
Time Frame: baseline and 12 months
|
a serum biomarker of bone formation
|
baseline and 12 months
|
Fasting Plasma Glucose
Time Frame: baseline and 12 months
|
to be assessed by fasting blood drawn after 12 hour fast
|
baseline and 12 months
|
Serum Aspartate Transaminase (AST)
Time Frame: baseline and 12 months
|
to be assessed by blood drawn after 12 hour fast
|
baseline and 12 months
|
Alanine Transaminase (ALT)
Time Frame: baseline and 12 months
|
to be assessed by blood drawn after 12 hour fast
|
baseline and 12 months
|
Number of Participants With Symptoms and Any Adverse Events
Time Frame: between baseline and 12 months
|
Number of participants with symptoms and any adverse events
|
between baseline and 12 months
|
Appendicular Lean Mass (ALM)
Time Frame: baseline and 12 months
|
Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs
|
baseline and 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Handgrip Strength
Time Frame: baseline and 12 months
|
measure muscle strength and performance using grip strength dynamometer
|
baseline and 12 months
|
Isokinetic Leg Strength
Time Frame: baseline and 12 months
|
measure muscle strength and performance using Biodex Isokinetic Dynamometer
|
baseline and 12 months
|
Health Aging and Body Composition-Physical Performance Battery
Time Frame: baseline and 12 months
|
lower extremity performance score, scale from 0 (worst performance) to 4 (best performance)
|
baseline and 12 months
|
Serum Insulin Like Growth Factor-1 (IGF-1)
Time Frame: baseline and 12 months
|
anabolic intermediary of growth hormone
|
baseline and 12 months
|
Serum C-telopeptide (CTX)
Time Frame: baseline and 12 months
|
bone resorption marker
|
baseline and 12 months
|
Bone Mineral Density of the Spine and Hip
Time Frame: baseline and 12 months
|
assessed by DXA
|
baseline and 12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Bess Dawson-Hughes, MD, Tufts University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 5, 2019
Primary Completion (Actual)
January 26, 2023
Study Completion (Actual)
January 26, 2023
Study Registration Dates
First Submitted
July 9, 2019
First Submitted That Met QC Criteria
July 15, 2019
First Posted (Actual)
July 16, 2019
Study Record Updates
Last Update Posted (Actual)
March 27, 2024
Last Update Submitted That Met QC Criteria
February 27, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3035
- 1R21AR074138-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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