A Study to Evaluate a Skeletal-muscle Microbiopsy Technique With Dynamic Proteomic Measurement in Healthy Male Volunteers

NCT01962454 | Completed Phase 1

• 1 other identifier: 200030
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Cachexia

Keywords

muscle mass; dynamic proteomics; Duke University; Microbiopsy; D2O; testosterone; skeletal muscle

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in muscle derived protein synthesis rate

  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.

  Baseline and Day 21

Secondary Outcomes (4)

• 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

• Changes in FSR in muscle and serum derived muscle proteins

  Baseline, Day 7, 14, and 21

• 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

Study Arms (2)

Arm 1

EXPERIMENTAL

Run-in Phase: All participants will receive oral deuterated water (D2O) for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50mL 70% D2O three times per day (TID) for 7 days, followed by a 50ml 70% D2O dose twice daily (BID) for the next 2 weeks. Treatment Phase: Subjects will receive testosterone matching placebo IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks.

Drug: Deuterated Water; Drug: Testosterone enanthate

Arm 2

PLACEBO COMPARATOR

Run-in Phase: All participants will receive oral D2O for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50 mL 70% D2O TID for 7 days, followed by a 50mL 70% D2O dose BID for the next 2 weeks. Treatment Phase: Subjects will receive testosterone IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks

Drug: Deuterated Water; Drug: Placebo to match testosterone enanthate

Interventions

Deuterated Water DRUG

D2O 70% will be supplied as clear liquid, provided in 50 millilitre (mL) unit dose vials; administered per orally.

Arm 1; Arm 2

Testosterone enanthate DRUG

Testosterone enanthate 125mg injection will be supplied as colorless to pale yellow liquid; administered intramuscular (IM).

Arm 1

Placebo to match testosterone enanthate DRUG

Placebo to match testosterone enanthate 0.625 mL injection will be supplied as greenish yellow, bright and clear oily liquid; administered intramuscular (IM).

Arm 2

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males aged between 60-75 of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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.
• Subjects with a history of clinically significant endocrine, gastrointestinal, cardiovascular, neurological, haematological, immunological, renal, respiratory, vertigo, dizziness, prostate enlargement, or genitourinary abnormalities or diseases
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of muscular or neuromuscular disease such as multiple sclerosis, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis, stroke or transient ischemic attack
• Hospitalization in the past 6 months
• Current or recent use of ACE-inhibitors and/or systemic steroids
• Diabetes (Type 1, Type 2)
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>14 drinks for males. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• History of sensitivity to any of the local anaesthetics, study diagnostic reagents, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• History of bleeding disorder, including thrombocytopenia and other coagulopathies, or current use of anti-coagulants.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Durham, North Carolina, 27705, United States

Location

Related Links

• Results for study 200030 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Cachexia

Interventions

testosterone enanthate

Condition Hierarchy (Ancestors)

Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thinness

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 14, 2013
• Study Start: May 5, 2014
• Primary Completion: March 20, 2015
• Study Completion: March 20, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)