Cachexia
Conditions
Keywords
muscle mass, dynamic proteomics, Duke University, Microbiopsy, D2O, testosterone, skeletal muscle
Brief summary
This is a single-blind, randomized placebo-controlled, parallel study, where the study volunteers will be blinded to testosterone/placebo treatment. This study will test a relatively new, less invasive method for collecting muscle tissue to determine if this method is appropriate for collecting muscle samples for the assessment of the fractional synthetic rates (FSR) of muscle-derived proteins. This study will also investigate whether the FSR of proteins may serve as early biomarkers for muscle anabolism, a known anabolic agent (testosterone) will be administered to healthy, elderly male subjects over a 3 week period. The fractional synthetic rate of several muscle-derived proteins will be analyzed at Baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from deuterated water (D2O).
Interventions
DRUGDeuterated Water
D2O 70% will be supplied as clear liquid, provided in 50 millilitre (mL) unit dose vials; administered per orally.
DRUGTestosterone enanthate
Testosterone enanthate 125mg injection will be supplied as colorless to pale yellow liquid; administered intramuscular (IM).
DRUGPlacebo to match testosterone enanthate
Placebo to match testosterone enanthate 0.625 mL injection will be supplied as greenish yellow, bright and clear oily liquid; administered intramuscular (IM).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
60 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Males aged between 60-75 of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Ambulatory outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension and/or dyslipidemia. Subjects must be able to satisfactorily complete each lower extremity 1-repetition maximum leg press assessment. * Body weight \>=50 kilogram and body mass index within the range 20 - 34 kilogram per square meter (inclusive) * Renal clearance \>= 45 milliliter per minute based on estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated MDRD equation, using serum creatinine and demographic data obtained at Screening. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form * ALT, alkaline phosphatase and bilirubin =\< 1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Averaged corrected QT interval (QTc) values of 3 electrocardiograms separated by a 3-5 minute period: Bazett's QTc (QTcB) or Fridericia's QTc (QTcF) \< 460 msec; or QTcB or QTcF \< 480 msec in subjects with Partial Bundle Branch Block.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in muscle derived protein synthesis rate | Baseline and Day 21 | Muscle protein synthesis will be assessed by measuring the fractional synthetic rate of muscle-derived proteins in both muscle biopsy samples and in blood after subjects have ingested deuterated water. The FSR of several muscle-derived proteins will be analyzed at baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from D2O. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in lower extremity strength using the 1-repetition maximum (1-RM) leg strength, FSRs from muscle proteins derived from muscle biopsies and serum samples | Baseline, Day 7, 14, and 21 | Lower extremity strength will be measured as the 1-RM on a leg press device. Strength will be measured at baseline (Day 1, prior to start of testosterone) and at study end (Day 21). The FSR of several muscle-derived proteins will be analyzed at Baseline and during the period in both muscle biopsy samples and in blood after subjects have ingested deuterated water. |
| Changes in FSR in muscle and serum derived muscle proteins | Baseline, Day 7, 14, and 21 | The FSR of several muscle-derived proteins will be analyzed at Baseline and during the period in both muscle biopsy samples and in blood after subjects have ingested deuterated water. |
| Number of biopsy samples required to obtain desired collection weight | Baseline, Day 7, 14, and 21 | — |
| Number of participants with biopsy-related adverse events | Upto Week 7 | — |
Countries
United States
Outcome results
None listed