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Trial registered on ANZCTR
Registration number
ACTRN12622000480785p
Ethics application status
Not yet submitted
Date submitted
5/03/2022
Date registered
25/03/2022
Date last updated
26/05/2023
Date data sharing statement initially provided
25/03/2022
Type of registration
Prospectively registered
Titles & IDs
Public title
The Effect of Regular Exercise & Intermittent Rapamycin Dosing On Muscle Performance In Older Adults
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Scientific title
The Effect of Regular Exercise & Intermittent Rapamycin Dosing On Muscle Performance In Older Adults
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Secondary ID [1]
306604
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Nil known
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Universal Trial Number (UTN)
U1111-1279-0901
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Trial acronym
RAISE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
sarcopenia
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Condition category
Condition code
Musculoskeletal
322889
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0
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Other muscular and skeletal disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
This study is a test of an FDA-approved drug, Sirolimus (Rapamycin), being repurposed for the treatment of muscle aging in combination with exercise. The first phase is a proof-of-concept trial, designed to assess the safety, tolerability, feasibility, and trial design of weekly Sirolimus (Rapamycin) 6mg oral tablets or placebo dosing over a 13-week period, in combination with thrice-weekly at-home exercise programs. The trial will also assess improvement in the 30-Second Chair-Stand test after a 13-week exercise training program. This will enable an appropriate power calculation to be conducted to inform the number of patients required for a subsequent, superiority clinical trial.
Participants can be within 65-85 years of age at the time of enrolment, with either no co-morbidities or a well-controlled chronic condition, who do not already perform weekly, strenuous exercise. Participants will provide informed consent and undergo initial screening. If eligible, patients will be randomised in a 1:1 ratio to either the once-weekly placebo or Rapamycin group. In parallel to the oral medication, patients will engage three times a week in an at-home exercycle fitness program. The exercycles will be hired and delivered to the participants’ homes. Fitness-dependent exercise standardisation is important to minimise variance, particularly given that the primary outcome is a measure of exercise performance and can therefore be greatly influenced by the level of exercise training. To that end, here is the proposed exercycle training program:
Week 1: warm-up of 2 mins @ 50RPM, then 3 mins workout @70-80RPM @ very low resistance, then a cooldown of 2 mins @ 45RPM
Week 2: warm-up of 2 mins @ 50RPM, then 4 mins workout @70-80RPM @ very low resistance, then a cooldown of 2 mins @ 45RPM
Week 3: warm-up of 2 mins @ 50RPM, then 5 mins workout @70-80RPM @ very low resistance, then a cooldown of 2 mins @ 45RPM
Week 4: warm-up of 2 mins @ 50RPM, then 6 mins workout @70-80RPM @ very low resistance, then a cooldown of 2 mins @ 45RPM
Week 5: warm-up of 2 mins @ 50RPM, then 7 mins workout @70-80RPM @ low resistance, then a cooldown of 2 mins @ 45RPM
Week 6: warm-up of 2 mins @ 50RPM, then 8 mins workout @70-80RPM @ low resistance, then a cooldown of 2 mins @ 45RPM
Week 7: warm-up of 2 mins @ 50RPM, then 9 mins workout @70-80RPM @ low resistance, then a cooldown of 2 mins @ 45RPM
Week 8: warm-up of 2 mins @ 50RPM, then 10 mins workout @70-80RPM @ low resistance, then a cooldown of 2 mins @ 45RPM
Week 9: warm-up of 2 mins @ 50RPM, then 11 mins workout @70-80RPM @ medium resistance, then a cooldown of 2 mins @ 45RPM
Week 10: warm-up of 2 mins @ 50RPM, then 12 mins workout @70-80RPM @ medium resistance, then a cooldown of 2 mins @ 45RPM
Week 11: warm-up of 2 mins @ 50RPM, then 13 mins workout @70-80RPM @ medium resistance, then a cooldown of 2 mins @ 45RPM
Week 12: warm-up of 2 mins @ 50RPM, then 14 mins workout @70-80RPM @ medium resistance, then a cooldown of 2 mins @ 45RPM
Week 13: warm-up of 2 mins @ 50RPM, then 15 mins workout @70-80RPM @ medium resistance, then a cooldown of 2 mins @ 45RPM
All warm-ups and cooldown phases should be completed with a very low resistance setting.
If participants are unable to complete the exercycle training program due to difficulty, the program can be adjusted whereby the resistance setting is lowered. If a participant still cannot complete the training program, then they should aim to ride for as long as they can before moving to the cooldown phase.
In order to match the real-world setting, the exercycle program will not be supervised by a fitness instructor. Instead, when the exercycles are delivered, the participant will be shown how to use the exercycle and provided the exercise program as outlined above.
Patients will record their exercise program in an exercise diary, and it will include the length of training, the RPM, and the resistance setting.
To measure adherence, the Sirolimus (Rapamycin) will be blister-packed and the participants will complete an exercise diary. Both the medication packs and the exercise diary will be collected at the 6-week and 13-week intervals.
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Intervention code [1]
323031
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Prevention
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Intervention code [2]
323032
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Treatment: Drugs
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Intervention code [3]
323033
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Lifestyle
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Comparator / control treatment
The 20 participants in the control group will also complete the 13-week, thrice-weekly, at-home exercise program, but will take a matching placebo instead of the Sirolimus (Rapamycin) once a week. The matching placebo will be manufactured by CompoundLabs
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Control group
Placebo
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Outcomes
Primary outcome [1]
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General muscle performance as measured by the 30-Second Chair-Stand Test (30CST)
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Assessment method [1]
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Timepoint [1]
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The 30-Second Chair-Stand Test (30CST) will be measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [1]
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Handgrip strength as measured by a dynamometer
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Assessment method [1]
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Timepoint [1]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [2]
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General fitness assessed by the 6-minute walk test
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Assessment method [2]
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Timepoint [2]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [3]
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General balance assessed by the Community Balance & Mobility (CBM) scale
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Assessment method [3]
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Timepoint [3]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [4]
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Lean muscle mass as measured by a DEXA scan
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Assessment method [4]
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Timepoint [4]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [5]
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Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as calculated via the blood glucose and insulin levels (glucose x insulin ÷ 22.5)
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Assessment method [5]
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Timepoint [5]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [6]
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Full Blood Count
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Assessment method [6]
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Timepoint [6]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [7]
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Renal functions tests (serum Creatinine, Sodium, Potassium)
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Assessment method [7]
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Timepoint [7]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [8]
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Liver Function Tests - Serum Alanine transaminase (ALT), Alkaline phosphatase (ALP), Gamma-glutamyltransferase (GGT), Bilirubin, & Albumin
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Assessment method [8]
407136
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Timepoint [8]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [9]
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Serum Lipid Profile
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Assessment method [9]
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Timepoint [9]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [10]
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Serum Insulin-like growth factor 1 (IGF-1)
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Assessment method [10]
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Timepoint [10]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [11]
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DNA Methylation Clock (provided by TruDiagnostics) via blood sample
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Assessment method [11]
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Timepoint [11]
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Measured at baseline and after 13 weeks post commencing treatment.
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Secondary outcome [12]
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GlycanAge via blood sample
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Assessment method [12]
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Timepoint [12]
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Measured at baseline and 13 weeks post commencing treatment
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Secondary outcome [13]
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Quality of life assessed using the 36-Item Short Form Survey (SF-36)
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Assessment method [13]
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Timepoint [13]
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Measured at baseline and at 13 weeks post commencing treatment.
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Eligibility
Key inclusion criteria
• Males and females aged >=65 years and <=85 years at the time of signing informed consent
• Medically stable and do not already perform regular strenuous exercise
• Capable of providing written informed consent and willing and able to adhere to all protocol requirements
• Participants must be reliable, adherent, and agree to cooperate with all planned trial evaluations as explained in detail during the informed consent process and to be able to perform them.
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Minimum age
65
Years
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Maximum age
86
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
• Already participating in strenuous activity enough to cause a noticeable increase in breathing more than twice a week
• 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
• Older adults scheduled to undergo major surgery in the next 12 months
• Any uncontrolled or serious disease, or anything medical (e.g. known active infection or major haematological, renal, metabolic, gastrointestinal, or endocrine dysfunction) or surgical that, in the opinion of the investigator, may interfere with participation in the clinical study and/or put the patient at significant risk.
• Malignancy (except non-melanoma skin cancers, cervical carcinoma in-situ) within the last 5 years.
• Known hypersensitivity, allergy, or any contraindication to Rapamycin or its excipients
• Fibromyalgia or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Breast Implant Illness
• Congestive heart failure: self-assessed functional status of heart failure New York Heart Association (NYHA) classification III or IV
• COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification III or IV
• Impaired renal function, as defined as glomerular filtration rate eGFR < 30
• Type 1 or Type 2 Diabetes (HbA1c must be <50 mmol/mol)
• Substance, alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation leading to decreased compliance with trial procedures or study medication intake in the opinion of the investigator
• Psychological, familial, sociological, or geographic factors potentially hampering compliance with the protocol, visits, or trial procedures or any other clinical condition that would jeopardise patient safety while participating in the clinical trial in the opinion of the investigator
• Those who have taken metformin, Rapamycin, or rapalogs in the past 6 months
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
5/02/2024
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Actual
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Date of last participant enrolment
Anticipated
5/08/2024
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Actual
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Date of last data collection
Anticipated
7/10/2024
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Actual
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Sample size
Target
40
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Accrual to date
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Final
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Recruitment outside Australia
Country [1]
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New Zealand
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State/province [1]
24639
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Funding & Sponsors
Funding source category [1]
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Other Collaborative groups
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Name [1]
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VitaDao
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Address [1]
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Vitality Healthspan Foundation
3456 Paul Anka Drive. Ottawa, ON K1V 9K6
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Country [1]
310941
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Canada
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Funding source category [2]
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Other Collaborative groups
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Name [2]
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Lifespan.io
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Address [2]
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3805 Estella St., Seaford, New York, 11783
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Country [2]
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United States of America
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Primary sponsor type
Other Collaborative groups
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Name
Vitality Healthspan Foundation
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Address
3456 Paul Anka Drive. Ottawa, ON K1V 9K6
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Country
Canada
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Secondary sponsor category [1]
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None
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Name [1]
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Address [1]
312234
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Country [1]
312234
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Ethics approval
Ethics application status
Not yet submitted
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Ethics committee name [1]
310494
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Health and Disability Ethics Committee
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Ethics committee address [1]
310494
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Level 1 South Tower, 110 Symonds Street, Grafton, Auckland 1010
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Ethics committee country [1]
310494
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New Zealand
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Date submitted for ethics approval [1]
310494
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05/03/2024
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Approval date [1]
310494
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Ethics approval number [1]
310494
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Summary
Brief summary
Our brief hypothesis is that by having 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 Sirolimus (Rapamycin), this strategy will result in greater muscle performance in older adults compared with just exercise alone.
To explore this idea, we propose a 13-week, randomised, double-blind, placebo-controlled, Phase 2a Proof of concept trial of 40 participants, with 20 in the placebo arm and 20 in the Sirolimus (Rapamycin) arm. Participants will complete a thrice-weekly at-home exercise program. Medication will be taken once a week. Before the trial begins, exercycles will be delivered to the participant’s house, and once the trial begins the participants will complete a standardised exercycle program.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Dr Dr Brad Stanfield
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Address
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Tuakau Health Centre
55 George Street, Tuakau, Auckland, 2121
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Country
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New Zealand
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Phone
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+64210426045
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Fax
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Email
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[email protected]
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Contact person for public queries
Name
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Dr Dr Brad Stanfield
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Address
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Tuakau Health Centre
55 George Street, Tuakau, Auckland, 2121
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Country
117871
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New Zealand
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Phone
117871
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+64210426045
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Name
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Dr Dr Brad Stanfield
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Address
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Tuakau Health Centre
55 George Street, Tuakau, Auckland, 2121
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Country
117872
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New Zealand
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Phone
117872
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+64210426045
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Fax
117872
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Email
117872
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[email protected]
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Anonymised patient result data, demographic data, exercise diary data, adherence to placebo/Sirolimus data
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When will data be available (start and end dates)?
The data will be available after the trial is submitted to a clinical journal, and there will be no end date.
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Available to whom?
The data will be available upon reasonable request
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Available for what types of analyses?
Meta-analysis and auditing
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How or where can data be obtained?
Contact the trial co-principle investigator at
[email protected]
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What supporting documents are/will be available?
No Supporting Document Provided
Doc. No.
Type
Citation
Link
Email
Other Details
Attachment
15305
Study protocol
383703-(Uploaded-25-03-2022-05-47-00)-Study-related document.pdf
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.
Download to PDF