The Testosterone Trials in Older Men
Condition: Andropause
Intervention: AndroGel® (testosterone gel); Placebo
Intervention description: Testosterone levels will be measured at regular intervals in order to achieve a testosterone level in the desired range.; Testosterone levels will be measured at regular intervals.
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 790.0
Sex: Male
Minimum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Testosterone; Mobility disability; Decreased libido; Age associated memory impairment; Low vitality; Anemia

Summary:

      The Testosterone Trials are a multi-center set of trials involving 12 clinical sites
      geographically distributed across the United States.

      The primary specific aims are to test the hypotheses that testosterone treatment of elderly
      men whose serum testosterone concentrations are unequivocally low - and who have symptoms and
      objectively measured abnormalities in at least one of five areas that could be due to low
      testosterone (physical or sexual function, vitality, cognition, and anemia) - will result in
      more favorable changes in those abnormalities than placebo treatment.

      Two additional trials have been incorporated into the T Trial. Only men enrolled in the T
      Trial are eligible to participate in these trials.

        -  The Cardiovascular Trial will examine if testosterone treatment results in more
           favorable changes in cardiovascular risk factors, compared to placebo.

        -  The Bone Trial will test the hypothesis that testosterone treatment will increase
           volumetric trabecular bone mineral density (vBMD) of the lumbar spine as measured by
           quantitative computed tomography (QCT), compared with placebo treatment.

      A Pharmacokinetic (PK) Study is also being conducted within the context of the interventional
      T Trial. It will examine the variability of the serum testosterone (T) concentration after
      application of testosterone gel or placebo, four months after the start of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men greater than or equal to 65 years old

          -  Total serum testosterone concentration < 275 and < 300 ng/dL at 7 -10 AM at each of
             two screening visits

        Exclusion Criteria:

          -  Diagnosed prostate cancer, prostatic intraepithelial neoplasia (PIN), prostate nodule
             or, by the Prostate Cancer Risk Calculator, a >35% risk of having overall prostate
             cancer or >7% risk of having high grade prostate cancer

          -  Severe lower urinary tract symptoms (score of > 19) by the International Prostate
             Symptom Score questionnaire

          -  Hemoglobin <10 g/dL or >16.0 g/dL

          -  Sleep apnea, diagnosed but untreated

          -  Alcohol or substance abuse within the past year (based on self report)

          -  Angina not controlled by treatment

          -  NYHA class III or IV congestive heart failure

          -  Myocardial infarction within the previous 3 months before entry

          -  Stroke within the previous 3 months before entry

          -  Severe pulmonary disease that precludes physical function tests

          -  Serum creatinine >2.2 mg/dL; ALT 3x upper limit of normal; hemoglobin A1c >8.5%, TSH >
             7.5mIU/L

          -  Diagnosis or treatment for cancer within the past 3 years, with the exception of
             nonmelanotic skin cancer

          -  Body mass index (BMI) >37 kg/m2

          -  Mini Mental State Exam (MMSE) Score <24

          -  Major psychiatric disorders, including major depression (PHQ-9 score > 14), mania,
             hypomania, psychosis, schizophrenia or schizoaffective disorders, that are untreated,
             unstable, have resulted in hospitalization or medication change within the previous
             three months, or would result in inability to complete the trial efficacy instruments.
             Subjects whose disorders have been stable while being treated for more than three
             months are eligible.

          -  Use of the following medications within the previous three months:

               -  drugs that affect serum testosterone concentration

               -  rhGH or megestrol acetate

               -  introduction of anti-depressant medication

               -  daily use of prednisone for more than two weeks

          -  Opiate use within the past three months

          -  Skin conditions at the testosterone gel application site, such as ulcer, erosion,
             lichenification, inflammation, or crust, or generalized skin conditions such as
             psoriasis or eczema that might affect testosterone absorption or tolerability of the
             testosterone gel

          -  Known skin intolerance to alcohol or allergy to any of the ingredients of testosterone
             gel

        Participants in the T Trial may also enroll in the Cardiovascular and Bone Trials if it is
        determined that they are eligible based on the specific exclusion criteria.