Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by The University of Texas, Galveston
Sponsor:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT00957801
First received: August 10, 2009
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

Skeletal muscle loss is a common consequence of aging and in some individuals reaches a level that compromises health and quality of life. Age-associated increases in cytokine and inflammatory signaling may be important contributors to this process. In this project the investigators will test the hypotheses that 1) testosterone will inhibit cytokine and inflammatory signaling in skeletal muscles of older adults and 2) will augment the anabolic response to increased skeletal muscle activity. The investigators will also assess the practical question of whether testosterone injection and gel application elicit similar responses. Resistance exercise will be used as a means of stimulating both inflammatory and anabolic responses in skeletal muscle. In order to assess the effects of testosterone on these responses, fourteen subjects will perform resistance exercise on two occasions separated by 7 days. The first session will be performed prior to the initiation of testosterone therapy and the second session will be performed after receiving testosterone for 7 days.


Condition Intervention Phase
Sarcopenia
Drug: Testosterone injection
Drug: Testosterone gel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anabolic and Inflammatory Responses to Short-Term Testosterone Administration in Older Men

Resource links provided by NLM:


Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Muscle protein synthesis and breakdown with and without testosterone treatment following resistance exercise [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Serum and skeletal muscle cytokine levels and inflammatory signaling will be measured before and after a standardized bout of resistance exercise, both with and without testosterone treatment [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparison of anabolic response and inflammatory response in muscle treated with injected testosterone versus testosterone gel [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Testosterone injection
Testosterone enanthate given as a single 150 mg Intramuscular (IM) injection
Drug: Testosterone injection
150 mg single IM injection
Other Name: Testosterone enanthate
Active Comparator: Testosterone gel
Testosterone topical gel 10 mg administered daily for seven days
Drug: Testosterone gel
Testosterone gel 10 mg. administered topically daily for seven days
Other Name: Androgel

Detailed Description:

In this project we will study the acute response to testosterone treatment between two groups of seven subjects each, comparing two methods of administration (injection vs. topical gel) in a sequential fashion in order to obtain pilot information for a subsequent, randomized, blinded long-term investigation.

The first session will be performed prior to the initiation of testosterone therapy and the second session will be performed after receiving testosterone for 7 days. Because dietary intake, particularly protein intake, can influence muscle metabolism, subjects will be placed on standardized diets for the twenty four hour period preceding muscle metabolism studies in order to reduce the likelihood of skewed results due to variations in nutritional intake just prior to these studies. In addition, subjects will be asked to maintain a food intake diary for the three day period prior to metabolism studies in order to document dietary intake in the days leading up to muscle metabolism studies. Subjects will also be asked to complete a fatigue questionnaire at baseline and at the final study to assess perceived changes in fatigue between the two treatment groups over the treatment period. Subjects will also collect their urine over a twenty four hour period prior to baseline and final studies to measure cortisol levels, which can influence the rate of protein breakdown.

  Eligibility

Ages Eligible for Study:   60 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age: 60-85
  • Gender: Male

Exclusion Criteria:

  • Exclusionary medications will be an anticoagulant (Coumadin) because of the risk of bleeding during the biopsy procedure. Additional medications which will be disallowed for participation include: anabolic steroids, nitrates, antihistamines, and glucocorticoids.
  • The subjects must be able to successfully complete an exercise stress test using the Bruce protocol . Subjects will be excluded without exercise testing, with a history of angina that occurs with exertion or at rest, or a myocardial infarction within the last 12 months. Subjects that demonstrate ³0.1 milliVolts (mV) horizontal or downsloping ST segment depression, a drop in systolic blood pressure of ³10 mm Hg, and/or frequent or repetitive arrhythmias (defined as ³10 premature ventricular contractions (PVC)/min, or couplets) during the stress test will be excluded.
  • Subjects with LDL cholesterol above 200 mg/dL will be excluded .
  • Any man with a history of breast cancer or prostate cancer, or any indication of an occult carcinoma from an elevation of prostate specific antigen (PSA) above 4.0 mg/L (53), or severe benign prostatic hypertrophy (BPH) by history (frequent urination, reduced stream) will be excluded.
  • Subjects with liver dysfunction evidenced by a history of hepatitis B or hepatitis C, or by a three-fold elevation of liver enzymes (Alk phos, alanine aminotransferase (ALT), aspartate amino-transferase (AST) above normal on screening will be excluded from the study.
  • Any subject with a blood pressure on three consecutive measurements taken at one week intervals that has a systolic pressure ³ 140 or a diastolic blood pressure ³ 90 will be excluded.
  • Any subject who has a major medical illness such as diabetes, chronic obstructive pulmonary disease, or sleep apnea will be excluded. Moreover, subjects will not have a recent history of smoking tobacco. Morbidly obese older men (BMI > 35) will also be excluded.
  • Subjects will evidence of kidney disease (serum creatinine > 2.0mg/dl) will be excluded from participation.
  • Any subject with thyroid disease as determined by an abnormal thyroid stimulating hormone (TSH) level will be excluded from participation.
  • Any subject testing positive for HIV will be excluded .
  • Allergy to iodine, a component of Betadine which is used to prepare the subject's skin for invasive procedures, will be cause for exclusion from this study.
  • Men with serum total testosterone concentrations greater than 500 ng/dL will be excluded.
  • Subjects who engage in high intensity resistance training on a regular basis will be excluded.
  • Subjects with a known coagulation disorder or with clinical evidence indicative of a bleeding disorder (easy bruising, "free bleeders") will not be enrolled in this study due to potential problems that could arise from muscle biopsy procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957801

Contacts
Contact: Randall J Urban, M.D. (409) 772-1176 rurban@utmb.edu
Contact: Charles R Gilkison, RN,MSN (409) 772-2065 cgilkiso@utmb.edu

Locations
United States, Texas
The University of Texas Medical Branch at Galveston Recruiting
Galveston, Texas, United States, 77555-0567
Contact: Randall J Urban, M.D.    409-772-1176    rurban@utmb.edu   
Contact: Charles R Gilkison, RN,MSN    (409) 772-2065    cgilkiso@utmb.edu   
Sub-Investigator: Melinda Sheffield-Moore, Ph.D.         
Sub-Investigator: William Durham, Ph.D.         
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: Randall J Urban, M.D. The University of Texas Medical Branch at Galveston
  More Information

No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT00957801     History of Changes
Other Study ID Numbers: 09-070
Study First Received: August 10, 2009
Last Updated: May 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas, Galveston:
Sarcopenia
Aging muscle
Androgen
Cytokines
Muscle metabolism

Additional relevant MeSH terms:
Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Signs and Symptoms
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on July 20, 2014