SarcopeniaPhase 1NCT04021706
Effect of a Ghrelin Receptor Agonist on Muscle and Bone
A Phase 1 study testing Anamorelin Hydrochloride in people with Sarcopenia and Osteopenia, run by Tufts University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sarcopenia, Osteopenia
- What is being tested?
- Anamorelin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2019to 26 Jan 2023
- Phase
- Phase 1
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University
Boston, Massachusetts, 02111
About this study
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.
Read the 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.
- Conditions
- Sarcopenia, Osteopenia
- Being tested
- Anamorelin Hydrochloride, Placebo
- Medical subject headings
- Sarcopenia, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anamorelin HydrochlorideDrug
Ghrelin receptor agonist
PlaceboDrug
Also called microcrystalline cellulose
placebo is a inert substance
| Study group | Role | What they receive |
|---|---|---|
| anamorelin | Active comparator | one 100 mg tablet daily, taken one hour before breakfast Receives: Drug: Anamorelin Hydrochloride |
| microcrystaline cellulose | Placebo comparator | one identical appearing tablet daily, taken one hour before breakfast Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Body Muscle Mass
to be assessed by D3-creatine dilution
Measured: baseline and 12 months
Secondary outcomes (6)
Serum Procollagen 1 Intact N-terminal (P1NP)
a serum biomarker of bone formation
Measured: baseline and 12 months
Fasting Plasma Glucose
to be assessed by fasting blood drawn after 12 hour fast
Measured: baseline and 12 months
Serum Aspartate Transaminase (AST)
to be assessed by blood drawn after 12 hour fast
Measured: baseline and 12 months
Alanine Transaminase (ALT)
to be assessed by blood drawn after 12 hour fast
Measured: baseline and 12 months
Number of Participants With Symptoms and Any Adverse Events
Number of participants with symptoms and any adverse events
Measured: between baseline and 12 months
Appendicular Lean Mass (ALM)
Dual energy X-ray absorptiometry (DXA) lean mass of arms plus legs
Measured: baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start5 Dec 2019
- Primary completion26 Jan 2023
- Study completion26 Jan 2023
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 SarcopeniaStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind randomized controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Bess Dawson-Hughes, Tufts University
- Investigators
- Bess Dawson-Hughes, MD, Principal investigator, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021706
- Sponsor's protocol ID
- 3035
- Other IDs
- 1R21AR074138-01A1
- Status last verified
- Feb 2024
- First submitted
- 9 Jul 2019
- Last updated
- 27 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Ghrelin Receptor Agonist on Muscle and Bone
- ClinicalTrials.gov ID
- NCT04021706
- Acronym / sponsor ID
- 3035
- Conditions
- Sarcopenia, Osteopenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 5 Dec 2019 (actual)
- Primary completion
- 26 Jan 2023 (actual)
- Study completion
- 26 Jan 2023 (actual)
- First posted
- 16 Jul 2019 (actual)
- Results
- Posted 27 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind randomized controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| anamorelin | Active comparator | Drug: Anamorelin Hydrochlorideone 100 mg tablet daily, taken one hour before breakfast |
| microcrystaline cellulose | Placebo comparator | Drug: Placeboone identical appearing tablet daily, taken one hour before breakfast |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Ability to sign informed consent form
- Community dwelling individuals aged 50 years and older
- 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
Key exclusion criteria (29 listed)
- 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
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 |
|---|---|---|
| Anamorelin HydrochlorideGhrelin receptor agonist | Drug | anamorelin |
| PlaceboAlso: microcrystalline celluloseplacebo is a inert substance | Drug | microcrystaline cellulose |
Primary outcome
Total Body Muscle Mass
Time frame: baseline and 12 months
to be assessed by D3-creatine dilution
6 secondary outcomes
Serum Procollagen 1 Intact N-terminal (P1NP)
Time frame: baseline and 12 months
Fasting Plasma Glucose
Time frame: baseline and 12 months
Serum Aspartate Transaminase (AST)
Time frame: baseline and 12 months
Alanine Transaminase (ALT)
Time frame: baseline and 12 months
Number of Participants With Symptoms and Any Adverse Events
Time frame: between baseline and 12 months
Appendicular Lean Mass (ALM)
Time frame: baseline and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Bess Dawson-Hughes, MD principal investigator
Tufts University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anamorelin Hydrochloride in people with Sarcopenia and Osteopenia, run by Tufts University 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 7 inclusion and 29 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: finished, as of the sponsor's last update on 27 Mar 2024. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Mar 2024). 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?
Total Body Muscle Mass (time frame: baseline and 12 months). 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 27 Mar 2024.