Autonomic Manifestations of Testosterone Deficiency in Men

The primary goal of this pilot study is to investigate the association between testosterone deficiency and the presence of abnormalities in the function of the autonomic nervous system. If such association exists, then we will investigate the effect of testosterone replacement therapy on correcting these abnormalities.

Study Overview

• Status: Withdrawn
• Conditions: Male Hypogonadism; Autonomic Neuropathy

Detailed Description

The investigators will recruit 40 men between the ages of 40 to 80-years-old with low testosterone. Participants will be selected among those males referred to the Texas Tech University Health Sciences Center's (TTUHSC's) Internal Medicine Endocrinology Division outpatient clinic for the study and management of testosterone deficiency and to the TTUHSC Urology Department for diagnosis and management of prostate cancer that will result in testosterone deficiency due to surgical or pharmacological castration.

After recruitment, patients will have an initial standard clinical visit where aspects such as fatigue and anxiety will be investigated, followed by a full battery of autonomic testing (tilt table, heart rate response to deep breathing, Valsalva, and the Quantitative Sudomotor Axon Reflex Test (QSART).

Those patients with an initial diagnosis of testosterone deficiency will be initiated on testosterone replacement (intramuscular or skin routes) as standard of care, followed by a second visit in three (3) months--after normalization of serum testosterone levels--to evaluate changes in anxiety and fatigue level, and to repeat the cardiovascular autonomic function test.

Those patients with primary diagnosis of prostate cancer and normal serum testosterone levels will be evaluated a second time after confirmation of low testosterone, as described above. Standard questionnaires will be used to evaluate fatigue and anxiety. The autonomic testing of the heart will include tilt table (tilt the patient 70 degree by special designed table) and heart rate response to deep breathing, and Valsalva maneuver. Descriptive statistics will be compared between before and after treatment using different statistical methods.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Two groups will be recruited with 20 men in each group:

Group 1 will include 20 men between the ages of 40 to 80-years-old with symptoms and biochemical parameters of low testosterone.

Group 2 will include 20 men between the ages of 40 to 80-years-old with prostate cancer and normal serum testosterone that will be treated with surgical or pharmacological castration, as following standard of care at Urology Division, resulting in testosterone deficiency.

Description

Inclusion Criteria for first group:

1. Patients with testosterone deficiency (total testosterone< 277 ng/dL [9.6 nmol/L]) measured between 7-10 am, and with one or more symptoms and signs suggestive of androgen deficiency as mainly determined by history.

   • Reduced sexual desire (libido)
   • Decreased spontaneous erections
   • Breast discomfort, gynecomastia
   • Loss of body (axillary and pubic) hair - reduced shaving
   • Very small (<5ml) or shrinking testes
   • Height loss
   • Low trauma fracture
   • Low bone mineral density
   • Hot flushes
   • Sweats
   • Decreased energy
   • Decreased motivation
   • Decreased initiative
   • Decreased self confidence
   • Feeling sad or blue
   • Depressed mood
   • Dysthymia
   • Poor concentration
   • Poor memory
   • Sleep disturbance
   • Increased sleepiness
2. Age 40 to 80 years

Inclusion Criteria for second group:

1. Patients who underwent chemical or surgical castration for prostatic cancer who are going to receive androgen deprivation therapy.
2. Age 40 to 80 years

Exclusion Criteria (both groups):

1. Patients with history or current diagnosis of:

• Atrial fibrillation.
• Cardiac arrythmia
• Pacemaker placement.
• Myocardial infarction < 3 months
• Uncontrolled diabetes mellitus with hemoglobin A1c > 8.5% in the last 6 months.
• Diabetes mellitus with autonomic neuropathy
• Breast cancer
• Heart failure with left ventricular ejection fraction below 35%.
• Severe sleep apnea.
• Recent eye surgery (< 3 months)
• Recent ischemic stroke (< 3 months)
• History of retinal detachment.
• History of brain aneurysm.
• Severe chronic obstructive pulmonary disease (COPD) on oxygen therapy.
• Intraocular hemorrhage and lens dislocation.
• Glaucoma.
• Thyroid disease.
• Not literate in English

Exclusion Criteria for patient who will receive testosterone treatment

• Metastatic prostate cancer
• Prostate-specific antigen (PSA) concentration >4.0 mcg/L,
• Prostate-specific antigen (PSA) >3.0 mcg/L in high-risk men (African-Americans or men with first-degree relatives with prostate cancer). (Measured at clinic visit 1)
• Polycythemia (hemoglobin level >18 g/dL, hematocrit > 52%) (measured at clinic visit 1)
• Severe acne.
• History of venous or arterial thrombosis.
• Persons not literate in English

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
testosterone deficiency group; Men between the ages of 40 to 80-years-old with testosterone deficiency
prostate cancer group; Men between the ages of 40 to 80-years-old with prostate cancer that will result in testosterone deficiency due to surgical or pharmacological castration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with testosterone deficiency who will have abnormal autonomic function test (abnormal heart rate response to deep breathing, abnormal Valsalva ratio, and abnormal tilt table i.e. orthostatic hypotension).	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with testosterone deficiency and abnormal autonomic function test who will have such abnormalities corrected if they receive testosterone replacement therapy as part of standard of care.	24 months

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center
• Investigators: Principal Investigator: Ahmed M Eldokla, MD, Texas Tech Universty Health Science Center

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: March 17, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (ESTIMATE): March 22, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 18, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Autonomic neuropathy, Testosterone Deficiency
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism
• Other Study ID Numbers: L16-059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED