Effect of a Ghrelin Receptor Agonist on Muscle and Bone

• Status: Suspended
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

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. The results of this trial will inform the design of a larger, definitive randomized trial designed to establish efficacy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Tufts University
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Criteria

Inclusion Criteria:

1. Ability to sign informed consent form

2. Community dwelling individuals aged 50 years and older

1. Men (who are sterile or agree to use contraception throughout the study)

2. Postmenopausal women (no menses for 5 years; early postmenopausal women are ineligible because their bone turnover rate is changing rapidly)

3. 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

4. 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

5. Mini-mental state examination (MMSE) score >21

Exclusion Criteria:

1. BMI > 30 kg/m2 (obese are ineligible because anamorelin may cause weight gain)

2. 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])

3. Current participation in a fitness program or weight loss program

4. Advanced knee osteoarthritis (OA) or other conditions preventing strength or function testing

5. Lower extremity fracture in the last year

6. Diabetics taking insulin or sulfonylureas and subjects with a fasting blood sugar on screening >150 mg/dl

7. Inadequate hepatic function defined as AST and ALT levels > 2 x upper limit of normal at screening (>74 and >68 MU/ml, respectively)

8. Untreated thyroid or parathyroid disease

9. Significant immune disorder

10. eGFR<30 ml/min

11. Any clinically meaningful electrocardiogram (ECG) abnormality on screening or baseline

12. Crohn's disease

13. Active malignancy or cancer therapy in the last year

14. 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)

15. Allergy to components of the study interventions

16. Other condition or abnormality in screening labs at discretion of the study physician (the PI)

17. Medications:

1. Osteoporosis treatment - teriparatide, abaloparatide, raloxifene, denosumab, or romosozumab in the last 12 mo or a bisphosphonate in the last 2 years

2. Tamoxifen in the last 6 mo

3. Cancer treatment in the last 3 years (except basal cell skin cancer)

4. strong CYP3A4 inhibitors within the previous two weeks (ketoconazole, clarithromycin, itraconazole, nefazodone, telithromycin)since anamorelin is mainly metabolized by CYP3A4

5. 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)

6. Drugs with high affinity to alpha-acid glycoprotein (AAG) and therefore with potential to displace anamorelin from binding (e.g., carvedilol, chlorpromazine)

7. Inhibitors of P-glycoprotein (e.g., verapamil, quinidine), and inhibitors of OATP1B3 (e.g., cyclosporine, rifampicin)

8. CYP3A4 inducers (e.g., rifampin)

9. Oral or IV glucocorticoids (>10 days in the last 3 mo)

10. Gonadal hormones (vaginal estrogen okay)

11. Drugs to promote weight loss or gain

12. TNF-α inhibitors (e.g., adalimumab, adalimumab-atto, certolizumab pegol, etanercept, etanercept-szzs, golimumab, infliximab)