Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000790549
Ethics application status
Approved
Date submitted
20/06/2024
Date registered
26/06/2024
Date last updated
26/06/2024
Date data sharing statement initially provided
26/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Rapamycin impact on muscle strength and endurance in older adults
Scientific title
A Single-Centre, Double-Blind, Randomized, Placebo-Controlled 2-Arm Study to Evaluate Safety and Efficacy of Intermittent Rapamycin On Muscle Strength and Endurance In Older Adults Following A 13-Week Exercise Program
Secondary ID [1] 312369 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcopenia 334161 0
Condition category
Condition code
Musculoskeletal 330832 330832 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a single-centre, double-blind, randomized, 2-arm, placebo-controlled, off-label assessment of Rapamycin (Sirolimus), used for the treatment of muscle ageing in combination with exercise.

This study is a post-marketing phase 2a trial. It aims to investigate the effects of a 13-week regimen combining weekly 6mg doses of rapamycin or placebo with a thrice-weekly exercise program (exercycle +30-second chair stand).

Over a 13 week period:
Rapamycine - once weekly 6mg dose. Oral tablet
Placebo - once weekly dose. Oral tablet
Treatments will be provided in blister packs. Used blister packs will be returned to the trial site for reconciliation. Treatment will also be monitored using the patient diary..
At-home exercise regime: 3x per week - 30-second chair stand + exercycle program (starting (week 1) at low resistance for 10 min, building to (week 13) high resistance for 25 min (each workout also includes 2 min warm up and 2 min cooldown) - exercise regime is completed in the participants home. All participants are provided with the same exercycles to standardise the regime. Participants will complete a diary to record exercise adherence and alterations. Site staff will perform weekly contact calls to check participant adherence.

Week Warm-up Training Cooldown
1 2 min @ 50RPM 10 min @70-80RPM, resistance level 1 2 min @ 45RPM
2 2 min @ 50RPM 15 min @70-80RPM, resistance level 1 2 min @ 45RPM
3 2 min @ 50RPM 20 min @70-80RPM, resistance level 2 2 min @ 45RPM
4 2 min @ 50RPM 25 min @70-80RPM, resistance level 2 2 min @ 45RPM
5 2 min @ 50RPM 25 min @70-80RPM, resistance level 3 2 min @ 45RPM
6 2 min @ 50RPM 25 min @70-80RPM, resistance level 3 2 min @ 45RPM
7 2 min @ 50RPM 25 min @70-80RPM, resistance level 4 2 min @ 45RPM
8 2 min @ 50RPM 25 min @70-80RPM, resistance level 4 2 min @ 45RPM
9 2 min @ 50RPM 25 min @70-80RPM, resistance level 5 2 min @ 45RPM
10 2 min @ 50RPM 25 min @70-80RPM, resistance level 5 2 min @ 45RPM
11 2 min @ 50RPM 25 min @70-80RPM, resistance level 5 2 min @ 45RPM
12 2 min @ 50RPM 25 min @70-80RPM, resistance level 5 2 min @ 45RPM
13 2 min @ 50RPM 25 min @70-80RPM, resistance level 5 2 min @ 45RPM

All participants are given the same exercise regime but are able to adjust the regime to complete exercises to the best of their abilities, and document changes in the patient diary.
Intervention code [1] 328869 0
Prevention
Intervention code [2] 328887 0
Treatment: Drugs
Comparator / control treatment
Placebo (cellulose powder in a #000 sized empty gelatin capsules)
Control group
Placebo

Outcomes
Primary outcome [1] 338601 0
Evaluate the effect of Rapamycin on muscle strength and endurance in an older population following an exercise program.
- This is a composite primary outcome of muscle strength and endurance.
Timepoint [1] 338601 0
Measured at Baseline, Day 42 (+/-7), Day 91 (+7, primary endpoint)
Secondary outcome [1] 436541 0
To investigate the safety and tolerability of low-dose Rapamycin in exercising older adults.
Timepoint [1] 436541 0
Measured at baseline, Day 42 (+/- 7), Day 91 (+7)
Secondary outcome [2] 436542 0
To investigate the safety and tolerability of low-dose Rapamycin in exercising older adults.
Timepoint [2] 436542 0
Measured at baseline, Day 42 (+/- 7), Day 91 (+7)
Secondary outcome [3] 436543 0
To investigate the safety and tolerability of low dose Rapamycin in exercising older adults.
Timepoint [3] 436543 0
Baseline to End of Study
Secondary outcome [4] 436544 0
To evaluate change of muscle strength and muscle endurance from baseline to EOS.
Timepoint [4] 436544 0
Measured at Baseline, Day 42 (+/-7), and Day 91 (+7)
Secondary outcome [5] 436545 0
To evaluate change of muscle strength and muscle endurance from baseline to EOS.
Timepoint [5] 436545 0
Measured at Baseline and Day 91 (+7)
Secondary outcome [6] 436546 0
To evaluate change of muscle strength and muscle endurance from baseline to EOS.
Timepoint [6] 436546 0
Measured at Baseline, Day 42 (+/-7), and Day 91 (+7)
Secondary outcome [7] 436547 0
Participant reported outcomes
Timepoint [7] 436547 0
Measured at Baseline, Day 42 and Day 91 (+7)

Eligibility
Key inclusion criteria
1. Male or female aged between 65 years and 85 years at the time of signing informed consent
2. BMI between 18 and 40 and a maximum weight of 120kg at screening.
3. Currently sedentary lifestyle or performing moderate exercise for less than 15 mins, 3 times a week
4. Capable of providing written informed consent
5. Willing to swallow a #000 sized capsule
6. Willing and able to adhere to and comply with all study requirements, and attend all study visits
7. Able to complete the 30 second Chair Stand Test utilising correct technique
8. Is able to accommodate and use an exercycle at home for the duration of study participation
Minimum age
65 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

1. Anaemia - Hg < 9.0 g/dl, Leukopenia - white blood cells (WBC) < 3,500/mm3, Neutropenia - absolute neutrophil count < 2,000/mm3 , or Platelet count - platelet count < 125,000/mm3
2. Planned surgery during the period of the study that is likely to impact on ability to perform required study exercises
3. Any medical or psychological condition which in the opinion of the investigator, may interfere with the participants ability to and comply with the study requirements and/or put the participant at significant risk.
4. Impaired wound healing or history of a chronic open wound
5. Active infection at the time of signing consent or taking antibiotics or antifungal medications.
6. Malignancy (except non-melanoma skin cancers, cervical carcinoma in-situ) within the last 5 years.
7. Known hypersensitivity, allergy, or any contraindication to Rapamycin or placebo (cellulose powder) or its excipients
8. Fibromyalgia or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Breast Implant Illness, or other conditions that impact the participants ability to perform the exercise program
9. Known congestive heart failure with New York Heart Association (NYHA) classification III or IV
10. Prescribed substances that inhibit or induce CYP3A4 and/or P-glycoprotein (P-gp)
11. Current prescribed or reported cannabinoid use
12. COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification III or IV
13. Impaired renal function, as defined as glomerular filtration rate eGFR < 30
14. Type 1 diabetes or uncontrolled Type 2 Diabetes (defined as HbA1c = 60 mmol/mol)
15. Metformin, Rapamycin, or rapalogs use within 6 months prior to baseline.
16. Impaired hepatic function, measured by alkaline Phosphatase (ALP), alanine aminotransferase (ALT), Albumin, or T. Bili, whereby the levels are 1.5x greater than the normal upper limit.
17. Any form of clinically relevant primary or secondary immune dysfunction or deficiency (e.g. X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID))
18. Chronic oral corticosteroid or immunosuppressive medication use (e.g. Enbrel, Humira, methotrexate, ciclosporin).
19. Participation in any other study (for 30 days) prior to or during this study.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Centralised randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
block randomisation with stratification for age
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/07/2024
Actual
Date of last participant enrolment
Anticipated
5/09/2024
Actual
Date of last data collection
Anticipated
19/12/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 26391 0
New Zealand
State/province [1] 26391 0

Funding & Sponsors
Funding source category [1] 316777 0
Self funded/Unfunded
Name [1] 316777 0
Dr Brad Stanfield Ltd
Country [1] 316777 0
New Zealand
Primary sponsor type
Individual
Name
Dr Brad Stanfield Ltd
Address
Country
New Zealand
Secondary sponsor category [1] 318996 0
Other
Name [1] 318996 0
Vitasang
Address [1] 318996 0
Country [1] 318996 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315546 0
Northern B Health and Disability Ethics Committee 
Ethics committee address [1] 315546 0
https://ethics.health.govt.nz/about/northern-b-health-and-disability-ethics-committee/
Ethics committee country [1] 315546 0
New Zealand
Date submitted for ethics approval [1] 315546 0
11/04/2024
Approval date [1] 315546 0
17/06/2024
Ethics approval number [1] 315546 0

Summary
Brief summary
This study is a single-centre, double-blind, randomized, placebo-controlled, off-label assessment of Rapamycin (Sirolimus), used for the treatment of muscle aging in combination with exercise. Rapamycin is an approved product in multiple jurisdictions, including New Zealand (Medsafe approved) and the USA (FDA approved).

This study is designed as a randomized, double-blind, placebo-controlled, Phase 2a trial. It aims to investigate the effects of a 13-week regimen combining weekly 6mg doses of Rapamycin with a thrice-weekly exercise program. The primary objective is to evaluate whether this combined intervention is at least equivalent to regular exercise alone in enhancing muscle performance in older adults.

The primary endpoint measure is the change in the 30-second Chair-Stand Test (30CST). This test is critically selected for its ability to accurately evaluate functional muscle performance in the elderly. The study will compare muscle strength and endurance changes in the Rapamycin and exercise arm against the placebo and exercise arm. The study data will be used to determine whether the addition of Rapamycin diminish exercise benefits.

Adults aged between 65-85 years, who currently have a sedentary lifestyle, who do not perform moderate regular exercise (defined as less than 15 minutes of exercise, three times a week). Participants who provide informed consent, and meet the inclusion and exclusion requirements, will be randomized 1:1 to either the Rapamycin arm or the placebo arm.

Participants will engage in a standardized at-home chair-stand and exercycle fitness program, conducted three times a week. Exercycles will be provided by the study and delivered to participants' homes to ensure a consistent exercise regimen. This standardization is crucial for minimizing variability, as the primary outcome is heavily influenced by the level of exercise training.

To measure treatment and dose adherence, the Rapamycin will be blister-packed. Both used and unused blister-packs must be returned to the site and collected at the 6-week and 13-week interval for investigational product reconciliation.

Hypothesis
Periods of time where the mechanistic target of Rapamycin (mTOR) pathway is activated via exercise, combined with alternate periods of time where mTOR is inhibited using Rapamycin (Sirolimus), will result in greater muscle performance in older adults compared with just exercise alone.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135038 0
Dr Joanna Wojciechowska
Address 135038 0
Aotea Clinical Trials, 100 Hospital Rd, Auckland, 2025
Country 135038 0
New Zealand
Phone 135038 0
+64 9 270 9758
Fax 135038 0
Email 135038 0
Joanna.Wojciechowska@middlemore.co.nz
Contact person for public queries
Name 135039 0
Joanna Wojciechowska
Address 135039 0
Aotea Clinical Trials, 100 Hospital Rd, Auckland, 2025
Country 135039 0
New Zealand
Phone 135039 0
+64 9 270 9758
Fax 135039 0
Email 135039 0
info@aotearoatrials.nz
Contact person for scientific queries
Name 135040 0
Joanna Wojciechowska
Address 135040 0
Aotea Clinical Trials, 100 Hospital Rd, Auckland, 2025
Country 135040 0
New Zealand
Phone 135040 0
+64 9 270 9758
Fax 135040 0
Email 135040 0
info@aotearoatrials.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Anonymised patient result data, demographic data, exercise diary data, adherence to placebo/Sirolimus data
When will data be available (start and end dates)?
The data will be available after publication in a clinical journal. no specific end date.
Available to whom?
The data will be available upon reasonable request
Available for what types of analyses?
Meta-analysis and auditing
How or where can data be obtained?
Contact the sponsor brad@drstanfield.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.