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Testosterone and Pain Sensitivity

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Johns Hopkins University
Sponsor:
Collaborator:
Endo Pharmaceuticals
Information provided by (Responsible Party):
Adrian S. Dobs, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01689896
First received: September 11, 2012
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This research is being done to see whether testosterone replacement in men who take opioid-based pain medications and have low testosterone levels will show improvement in pain tolerance, pain perception and quality of life.

Some men who take opioid-based medications (narcotics) for pain develop low testosterone levels. Research has shown that low testosterone levels may make a person more sensitive to pain. This means that if a person with a painful condition develops low testosterone level as a result of his pain medications, he might become more sensitive to pain and so may need higher doses of pain medications for pain control.

Testosterone is a male hormone that is important for sperm production and the development of male characteristics such as muscle mass and strength, fat distribution, bone mass and sex drive. Testosterone hormone replacement therapy has been used for decades to treat men with low testosterone levels (male hypogonadism). Testosterone replacement therapies are available in the form of an injection into the muscle, implants under the skin, oral capsules taken by mouth, topical gels applied to the skin, and skin patches.

This study will use Fortesta®, a topical testosterone gel (T-gel) absorbed into the skin. Fortesta® is currently on the market as an FDA-approved treatment of male hypogonadism (low testosterone levels).

Men with non-cancer related pain who take opioid-based medications for pain and have low testosterone levels may join this study. (A low testosterone level is defined as early morning (before noon) blood testosterone level of 300 ng/dl or less, or a free testosterone of 50 ng/dl or less)).


Condition Intervention Phase
Low Testosterone
Hypogonadism
Pain
Drug: Testosterone Gel
Drug: Placebo Gel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Pain Tolerance - CPT [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    Cold Pressor Test: Participants will undergo a standard cold pressor task consisting of immersion of the right hand in a 4°C circulating water bath. The standardized instructions for the procedure will direct participants to keep their hands in the water for as long as possible but if the sensations become intolerable participants can remove their hands at any time. At the conclusion of the trial, participants will provide 0-100 ratings of the maximum intensity and unpleasantness of pain produced by water immersion during the trial. During the immersion trial, the time to cold pain threshold (CPTH), pain intensity and tolerance (CPTO) will be recorded.

  • Pain Tolerance - PPT [ Time Frame: 18 Weeks ] [ Designated as safety issue: No ]
    Pressure Pain Test: A Somedic algometer will be used to assess responses to noxious mechanical pressure. Pressure is increased steadily at a constant rate until the subject responds by pressing a button, at which point stimulation is terminated. Pressure pain thresholds and tolerances will be assessed 2 times each at 3 body sites bilaterally (the order of which will be randomized): trapezius muscle, masseter muscle, biceps femoris muscle, and ulnar area. For trials of pressure pain threshold, subjects indicate when the stimulus "first feels painful" and for trials of pressure pain tolerance, subjects are asked to respond when the stimulus "becomes intolerable."

  • QOL [ Time Frame: 18 Weeks ] [ Designated as safety issue: No ]
    Quality of Life: This parameter will be evaluated using Short Form-36 (SF-36) questionnaire.

  • Pain Tolerance - TPPT [ Time Frame: 18 Weeks ] [ Designated as safety issue: No ]

    Thermal Pain Perception Test: Contact heat stimuli will be delivered using a Medoc Thermal Sensory Analyzer, a peltier-element-based stimulator, with the 9 cm2 contact probe applied to the left forearm. The initial thermal assessment procedures include sampling of heat pain thresholds and heat pain tolerances using an ascending method of limits paradigm with a rate of rise of .5°C /Sec.

    Following, a series of 3 temporal summation procedures will be administered. Sequences of 10 rapid heat pulses are to be applied to the left volar forearm. Target temperatures will be based on subjects' individualized pain thresholds. Subjects will verbally rate the painfulness of each thermal pulse on a 0-100 (0= "no pain", 100= "most intense pain imaginable") rating scale. Subjects will be able to terminate the procedure at any time; for those who do, value equivalents to the final rating preceding termination will be assigned to the remaining trials for statistical analysis.



Secondary Outcome Measures:
  • Hormonal Outcomes [ Time Frame: 18 Weeks ] [ Designated as safety issue: No ]
    Serum will be obtained for serum total and free testosterone, estradiol, prolactin, SHBG, DHEA, FSH, and LH. Bone markers in the form of spot urine N-telopeptides, bone-specific alkaline phosphatase and osteocalcin will be checked, as a measure of bone turnover.


Estimated Enrollment: 70
Study Start Date: August 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Testosterone Gel
Testosterone Gel
Drug: Testosterone Gel
Other Name: Fortesta®
Placebo Comparator: Placebo Gel
Placebo Gel
Drug: Placebo Gel

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men
  • 18 Years of Age and Older
  • Serum total testosterone level <300 ng/dl or free testosterone < 50 pg/ml
  • Consumption of at least 10 mg of hydrocodone (or analgesic equivalent of another opioid) for at least 4 weeks
  • Absence of hospitalization in past 2 months
  • No acute illness in past 2 months
  • No prior history of any form of hypogonadism
  • No current anabolic therapy (growth hormone, DHEA, etc)
  • No current use or consumption in past 2 months of glucocorticoids and melatonin
  • Normal digital rectal examination
  • Normal PSA level

Exclusion Criteria:

  • Liver enzymes >3 times upper limit of normal
  • Serum creatinine > 2 times upper limit of normal
  • Neurological disease
  • Active psychiatric illness
  • Any addictive and/or illicit drug use
  • Alcoholism (>10 drinks/week)
  • Patients currently receiving glucocorticoids, melatonin or anabolic agents
  • Hospitalization in past 2 months
  • Acute illness in past 2 months
  • Consumption of < 20 mg of hydrocodone (or analgesic equivalent of another opioid)
  • Severe BPH
  • PSA >4.0 ng/ml
  • Prostate cancer
  • Breast cancer
  • Any cancer or cancer related pain
  • History of alcohol abuse
  • Known peripheral neuropathy (any etiology) or peripheral vascular disease (including Raynaud's disease), which may interfere with pain testing
  • Concurrent warfarin treatment
  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: NCT01689896

Locations
United States, Maryland
Johns Hopkins Medical Institutions Recruiting
Baltimore, Maryland, United States, 21205
Contact: Oyinkan Kusemiju, MPH    410-955-2812    Okusemi1@jhmi.edu   
Sponsors and Collaborators
Johns Hopkins University
Endo Pharmaceuticals
  More Information

No publications provided

Responsible Party: Adrian S. Dobs, Professor of Medicine and Oncology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01689896     History of Changes
Other Study ID Numbers: NA_00070640
Study First Received: September 11, 2012
Last Updated: September 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Hypogonadism
Low testosterone
Pain

Additional relevant MeSH terms:
Hypogonadism
Endocrine System Diseases
Gonadal Disorders
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents
Androgens
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014