The Effects of Long Term Cyclic Testosterone Administration on Muscle Function and Bone in Older Men
The general hypothesis is that administration of testosterone to healthy, older men for 52 weeks (1 year) following a cycle of 4 weeks of testosterone administration and 4 weeks without testosterone (i.e., monthly cycled regimen) will provide the same gains in muscle strength, muscle mass, and bone density as standard of care (SOC), continuous administration of testosterone for 52 weeks.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Effects of Long Term Cyclic Testosterone Administration on Muscle Function and Bone in Older Men|
- Muscle Strength [ Time Frame: 1 year ] [ Designated as safety issue: No ]Muscle strength will be measured using a Biodex 4. All strength measures will be normalized by dividing absolute strength by lean muscle mass.
- Lean Body Mass and Muscle Volume [ Time Frame: 1 year ] [ Designated as safety issue: No ]Lean body mass will be determined by DEXA and muscle volume by MRI.
- Bone density [ Time Frame: 1 year ] [ Designated as safety issue: No ]Bone density will be determined by DEXA.
- Assessment of risk factors [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Prostate health Complete Blood Count (CBC)/hypertension Serum estradiol Bone fracture risk.
- Assessment of Physical Performance [ Time Frame: 1 year ] [ Designated as safety issue: No ]Subjects will complete a timed 400 Molecular Weight (400MWT) at each study session to assess changes in gait speed as a proxy for physical function. In addition subjects will complete Patient Reported Outcomes Information System (PROMIS®) Short Forms addressing questions related to general health, fatigue, and physical functioning
- Assessment of muscle signaling [ Time Frame: 1 year ] [ Designated as safety issue: No ]Testosterone can alter skeletal muscle cell signaling. We will measure changes in key signaling proteins in skeletal muscle tissue. We anticipate that testosterone treatment will increase levels of anabolic signaling proteins and suppress levels of catabolic signaling proteins
- Assessment of bone metabolism. [ Time Frame: 1 year ] [ Designated as safety issue: No ]Testosterone can decrease rates of bone turnover (net increase of bone formation). We will measure changes in serum markers of bone formation and bone resorption.
- Assessment of Inflammation [ Time Frame: 1 year ] [ Designated as safety issue: No ]Testosterone is protective against inflammation. We will measure concentrations of cytokines in blood and muscle tissue.
- Assessment of cardiac stiffness [ Time Frame: 1 year ] [ Designated as safety issue: No ]Cardiac stiffness and relaxation will be assessed using echocardiography.
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Testosterone weekly injections continuously
Testosterone enanthate 100 mg Intramuscular (IM) weekly injections throughout the study
Drug: Testosterone enanthate
100 mg. IM weekly throughout study
Experimental: Cyclic testosterone administration
Testosterone injections 100 mg. IM weekly for one month alternating with placebo injections weekly for one month throughout the study
Drug: Testosterone enanthate
100 mg IM weekly for one month alternating with placebo injections for one month throughout the study
Placebo Comparator: Placebo injections
Placebo injections weekly throughout the study.
Injected IM weekly throughout study
The hypothesis is based on data from our current NIA-funded R01 protocol. The investigators treated older men with weekly intramuscular injections of testosterone enanthate (100 mg) for 4 weeks followed by 4 weeks of placebo injections. This 4-week-on, 4-week-off cycled treatment regimen was repeated for 5 cycles (20 weeks). This group was compared with a group of older men who received SOC weekly intramuscular injections of testosterone enanthate (100 mg) for 20 weeks, and another group who received placebo injections. Our preliminary data showed equal gains over placebo in muscle strength and lean body mass in those who received testosterone for 20 weeks, whether SOC continuous or cycled. Moreover, both groups showed greater bone density and markers of bone formation over placebo. In terms of the anabolic actions of testosterone on skeletal muscle in the older men, the investigators found that continuous and cycled administration of testosterone primarily stimulated muscle protein synthesis for the 20 weeks of the study. Cycled testosterone administration enhanced muscle protein synthesis throughout the full 5 cycles of 20 weeks, with no significant loss in muscle protein synthesis during the off-cycle weeks. Additionally, cycled and continuous testosterone administration reduced serum markers of bone resorption compared with placebo. These exciting findings of the benefits of a cycled testosterone regimen in older men represent a novel therapeutic paradigm over the existing SOC approach of continuous administration. The investigators believe the cycled regimen offers a more safe and efficacious approach to combat sarcopenia and osteoporosis with equal anabolic benefit to muscle and bone with only half the dose of testosterone. Critical to the application of this significant paradigm shift in testosterone administration is to determine whether these effects at 20 weeks can persist for the 52 weeks proposed in this study, which represents a treatment duration applicable to the traditional SOC approach.
Thus, the central hypothesis is that cycled administration of testosterone for 52 weeks in healthy, older men will increase muscle function as determined by muscle strength measurements (Biodex dynamometer), lean body mass (DEXA) and muscle volume (MRI), and bone density (DEXA) similar to SOC continuous testosterone administration. Moreover, the investigators anticipate reduced side effects of testosterone administration in the cycled group since they will receive one half the dose over the 52 weeks. The investigators will test the following specific hypotheses in healthy older adults during 52 weeks of cycled, continuous, or placebo testosterone:
- Cycled and continuous testosterone will increase muscle strength of upper and lower extremities compared with placebo as determined by Biodex dynamometer assessment.
- Cycled and continuous testosterone will increase lean body mass and muscle volume compared with placebo as determined by DEXA and MRI.
- Cycled and continuous testosterone will increase bone density compared with placebo as determined by DEXA. The following specific aims will be tested in a randomized double-blind placebo-controlled trial in healthy, older men (60-75 years) undergoing 52 weeks of cycled, continuous, or placebo testosterone:
1. To determine if cycled and continuous testosterone administration increases muscle strength compared to placebo. 2. To determine if cycled and continuous testosterone administration increases lean body mass and muscle volume compared to placebo. 3. To determine if cycled and continuous testosterone administration increases bone density compared to placebo. Our overall goal is to complete a long-term study to determine whether cycled testosterone achieves the same gains in muscle and bone function in older men as SOC, continuous testosterone administration. If our hypothesis is correct, then the investigators will validate an important paradigm shift in testosterone administration in older men that will help combat the disability of sarcopenia and osteoporosis using half the dose of testosterone of the current SOC approach. This reduction is testosterone dose should lessen the side effects and improve the safety of testosterone administration in healthy older men requiring androgen therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01417364
|Contact: Charles R Gilkison, RN, MSN||(409) firstname.lastname@example.org|
|Contact: Kate M Randolph, BS||(409) email@example.com|
|United States, Texas|
|The University of Texas Medical Branch, Galveston||Recruiting|
|Galveston, Texas, United States, 77555|