Testosterone and Physical Function in HIV+ Men

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborator: Charles Drew University of Medicine and Science
• Information provided by (Responsible Party): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Description

Brief Summary:

Men infected with the HIV virus (the virus that causes AIDS) often lose weight even though they may try to eat more food to gain weight. The reasons for this weight loss are not clear. Many men with HIV have low levels of testosterone in their blood. Testosterone is a hormone that is naturally produced in the bodies of both men and women and has important effects on building muscle and bone mass. The purpose of this study is to find out if providing additional testosterone to HIV infected men who have low testosterone can help them gain weight, increase their muscle mass, and feel better. The study will also help see if testosterone improves the efficiency with which your body produces and uses energy including fat. The dose of testosterone being used in this study will raise testosterone levels in the blood to higher than normal levels (2-3 times normal level).

Condition or disease	Intervention/treatment	Phase
HIV Associate Weight Loss	Drug: Testosterone enanthate; Drug: Placebo	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	61 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Other
Official Title:	Testosterone and Physical Function in HIV Associate Weight Loss
Actual Study Start Date :	May 2003
Actual Primary Completion Date :	June 2006
Actual Study Completion Date :	June 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: Testosterone enanthate; 300 mg of testosterone enanthate by intramuscular injection once weekly for 16 weeks	Drug: Testosterone enanthate
Placebo Comparator: Placebo; Placebo (sesame oil) by intramuscular injection once weekly for 16 weeks	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Stair climb [ Time Frame: 16 weeks ]
   A modification of the Margaria stair climb was used to assess stair-climbing power. participants were instructed to ascend a 12-step staircase as rapidly as possible, with ascent time recorded over the middle four steps (0.66 m) of the climb.
2. Walking speed [ Time Frame: 16 weeks ]
   Participants were instructed to walk a 160-m flat course as fast as possible without running. Photoelectric cells and timers were used to determine time to the nearest 0.01 s. The faster of two trials was used to calculate walking speed (m/s).
3. Load carry [ Time Frame: 16 weeks ]
   To simulate daily activities such as carrying groceries or suitcases, participants carried a load equal to 20% of their body weight while walking a distance of 20 m as fast as possible on a flat course.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• HIV positive men, 18-60 years of age, with objective evidence of HIV-infection with low to low-normal testosterone levels (<400 ng/dL). In boys before the age of 18, the hormonal and body composition changes of puberty can confound the data. We will exclude men over 60 because of age-related changes in testosterone levels and body composition, and increased risk of prostate disease.
• Documented weight loss within the previous 6 months of between 5-15% of body weight, or an actual body mass index (BMI) at screening of between 17 and 20 (= 85-95% of the lower limit of ideal weight).
• An energy intake of at least 80% of the estimated requirements. On stable and potent antiretroviral therapy for at least 12 weeks, and in whom, in the opinion of the primary care provider, a change in antiretroviral therapy is unlikely in the next 4 months. Stable therapy may include those not on any antiretroviral therapies and whom, in the opinion of the primary care provider, will not be starting antiretroviral therapy in the next 4 months CD4 cell count >50 /mm3, and HIV-copy number less than 10,000 copies/ml Testosterone levels <400ng/dL Able and willing to provide informed consent and comply with the protocol

Exclusion Criteria:

• Concurrent severe lipodystrophy* according to the patient and the investigator, defined as "the new appearance of thin extremities due to loss of subcutaneous fat (especially the medial compartment of the thigh) along with the new appearance of prominent veins. Loss of tissue in the buccal fat pad and subgluteal region provides further evidence that thin extremities may be in large part due to loss of fat and not just muscles."
• History of prostatic or mammary cancer
• Significant diarrhea defined as 6 or more stools per day with recent change in bowel habits towards more frequent stools, especially if associated with weight loss and fever
• Use of any androgen, growth hormone, or other anabolic or orexigenic agents within the past 6 months
• Use of systemic corticosteroids, except for topical application
• Significant cardiac, renal, hepatic or other diseases that, in the opinion of the Investigator, may put the subject at risk if entered onto the trial or prevent successful completion of the trial.
• AIDS defining illness (CDC HIV Classification, 1993: Clinical Category C) within the previous 3 months (except HIV wasting syndrome)
• Malignancy, other than Kaposi's Sarcoma localized to the skin
• Involvement in (vigorous) resistance exercise training programs (body building) in the past 3 months
• Diabetes mellitus Limiting neuromuscular, joint or bone disease, or history of stroke with residual neurological defect that would preclude measurements of muscle strength or physical function
• Severe symptoms of BPH (American Urological Association [AUA] symptom index score of >14), prostate nodule or induration on digital rectal examination (DRE) unless there has been a negative transrectal biopsy within 3 months, and prostate specific antigen (PSA) > 4
• Untreated severe obstructive sleep apnea, as assessed by Berlin's symptom score.
• Current alcohol or drug dependence which would interfere with compliance for the study
• Subject receive investigational treatment except stable antiretroviral investigational drug in the last 12 weeks
• Subject have a history of hypersensitivity to anabolic steroids or to growth hormone

• Any of the following blood test results:

  • Liver function test (ALT, AST) 5x the upper limit of the normal range (ULN)
  • Alkaline Phosphotase > 5x ULN or > 3x ULN if bilirubin is above normal
  • Cholesterol total (> 5 x ULN) or triglycerides 700 mg/dL
  • Serum Creatinine 2x ULN
  • Hemoglobin 8.0 g/dl or >18 g/dL
  • Platelet count < 50x109/L
  • HCT >48%
  • PSA 4 ng/ml.
• Concomitant Medications: Men who have received in the preceding 6 months or are currently using androgenic steroids, rhGH, IGF-I or other anabolic agents or appetite stimulants will be excluded. Also, excluded are drugs that affect testosterone secretion or metabolism such as ketoconazole, dilantin, and phenobarbital. Patients who have been on a stable dose of erythropoietin for at least 3 months will be allowed to continue the drug. The changes in antiretroviral therapy except for changes within the same class of drugs are not allowed. The use of corticosteroids, except for topical application, is not allowed. The food supplements that might affect body composition such as creatine, high dose amino-acid supplements, whey protein supplements, androstenedione, DHEA, and marinol, are also not allowed.
• On the Exclusion of Women. Women are not being included in this study because testosterone administration in these doses will inevitably cause virilization, and is ethically unacceptable.

Contacts and Locations

Locations

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United States, California
Charles R. Drew University
Los Angeles, California, United States, 90059

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Charles Drew University of Medicine and Science

Investigators

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Principal Investigator:	Shalender Bhasin, MD	Charles R. Drew University and Boston University Medical Center

More Information

Publications of Results:

Knapp PE, Storer TW, Herbst KL, Singh AB, Dzekov C, Dzekov J, LaValley M, Zhang A, Ulloor J, Bhasin S. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Am J Physiol Endocrinol Metab. 2008 Jun;294(6):E1135-43. doi: 10.1152/ajpendo.90213.2008. Epub 2008 Apr 22.

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Responsible Party:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00260143 History of Changes
Other Study ID Numbers:	DK49296 (completed); CDU IRB#: 00-11-153-04 ( Other Identifier: Charles R Drew University ); R01DK049296 ( U.S. NIH Grant/Contract )
First Posted:	December 1, 2005
Last Update Posted:	March 9, 2018
Last Verified:	March 2018

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

HIV+ men; Treatment Experienced

Additional relevant MeSH terms:

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Weight Loss; Body Weight Changes; Body Weight; Signs and Symptoms; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate	Methyltestosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents