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Completed

NCT Number: NCT00351819

Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

Naturally occurring opiates (endorphins) decrease testosterone levels by inhibiting the synthesis of gonadotropin releasing hormone (GnRH) and also inhibiting testosterone synthesis by the testes. Similarly, men with addiction to narcotics and those on exogenous opioids for pain control have decreased serum testosterone levels. Indeed, these men complain of decreased libido, erectile dysfunction and impaired quality of life. Animal studies have shown that gonadectomy results in a decrease in pain threshold in rats and repletion of testosterone elevates that threshold. These observations suggest that testosterone may possess analgesic properties. Hence, the investigators hypothesize that hypogonadism developing in men on opioids results in an increased sensitivity to pain and requirement of higher doses of opioids. In this study, the investigators plan to administer testosterone to men with opioid-induced hypogonadism and evaluate their pain perception, pain sensitivity in response to noxious stimuli and changes in the requirement of opioids in response to testosterone administration.

Hypothesis:

Testosterone replacement in men with opioid-induced hypogonadism will improve pain tolerance, pain perception and quality of life.

Specific aims:

1. To evaluate the effects of testosterone replacement on pain sensitivity, pain tolerance, and pain modulation in men with opioid-induced hypogonadism. 2. To determine the effects of testosterone replacement on health-related quality of life. 3. To determine whether testosterone replacement in hypogonadal men induces changes in the dosage requirements of opioid medications for pain control.

To accomplish our specific aims, the investigators propose a randomized, double blind, placebo-controlled, parallel arm study in which hypogonadal men with non-cancer chronic back pain syndrome on chronic opioids and low testosterone levels (<300 ng/dl) will be randomized to exogenous testosterone replacement therapy vs placebo. Our primary outcome is change in pain tolerance using various external painful stimuli. Secondary outcomes are change in pain sensitivity and modulation, quality of life and opioid requirements.

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Key information

Age range

18 year–100 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men
  • Age 18 years and older
  • Non-cancer chronic pain
  • Serum total testosterone level <350 ng/dl
  • Consumption of at least 20 mg of hydrocodone (or analgesic equivalent of another opioid) for at least 4 weeks
  • Absence of hospitalization in the past 2 months
  • No acute illness in the past 2 months
  • No current anabolic therapy (growth hormone, DHEA, etc)
  • No current use or consumption in the past 2 months of melatonin
  • Normal prostate exam
  • Normal PSA level

Exclusion criteria

  • Cancer-related chronic pain
  • Liver enzymes > 3 times upper limit of normal
  • Serum creatinine > 2 times upper limit of normal
  • Neurological disease
  • Active psychiatric illness
  • Any addictive drug use
  • Alcoholism (>3 drinks/day)
  • Patients currently receiving melatonin or anabolic agents
  • Hospitalization in the past 2 months
  • Acute illness in the 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

Treatment and study plan

AndroGel

Drug

5g gel, applied once daily to the upper arms, upper back or shoulders.

Other names: testosterone gel

Placebo

Other

5g gel, applied once daily to the upper arms, upper back or shoulders.

Primary outcomes

  1. Brief Pain Inventory (BPI) at Week 14

    Time frame: Week14 after intervention

    BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).

  2. Algometer-induced Pressure Pain at Week 14

    Time frame: Week 14 after intervention

    A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.

  3. Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14

    Time frame: Week 14 after intervention

    Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.

  4. Ice Water-induced Cold Pain and Its After-sensation at Week 14

    Time frame: Week 14 after intervention

    Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

Secondary outcomes

  1. Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14

    Time frame: Week14 after intervention

    IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.

  2. Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14

    Time frame: Week 14 after intervention

    The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.

  3. Pain Catastrophizing Scale (PCS) at Week 14

    Time frame: Values at week 14 after intervention

    PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.

Other outcomes

  1. Total Testosterone Values at Week 14

    Time frame: Week 14 after intervention

    Total testosterone was measured in a CDC-certified laboratory using an LC-MS/MS method with a sensitivity of 2 ng/dL.

  2. Free Testosterone Values at Week 14

    Time frame: Week 14 after intervention

    Free testosterone was calculated using a law of mass action equation.

  3. Sex Hormone Binding Globulin (SHBG) at Week 14

    Time frame: Week 14 after intervention

    Sex hormone binding globulin was measured using immunofluorometric assays, with limits of quantification of 2.5 nmol/L.

  4. Luteinizing Hormone Values at Week 14

    Time frame: Week 14 after intervention

    Luteinizing hormone was measured using immunofluorometric assays, with limits of quantification of 0.05 U/L.

  5. Inflammatory Cytokines at Week 14

    Time frame: Week 14 after intervention

    The pathophysiology of pain is measured by the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-Alpha).

  6. Body Composition at Week 14

    Time frame: Week 14 after intervention

    Body composition was measured using dual-energy X-ray absorptiometry scan.

  7. Lipid Profile at Week 14

    Time frame: Week 14 after intervention

    Serum total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol levels were measured by enzymatic assays and standardized to the CDC using the Lipid Research Clinic protocol. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation.

  8. HbA1c at Week 14

    Time frame: Week 14 after intervention

  9. Glucose Level in Oral Glucose Tolerance Test (OGTT) at Week 14

    Time frame: Week 14 after intervention

    All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The plasma glucose level were analyzed at baseline and at 60 and 120 min after glucose loading.

  10. Insulin Level in Oral Glucose Tolerance Test (OGTT) at Week 14

    Time frame: Values at week 14 after intervention

    All participants underwent 75-g oral glucose tolerance test (OGTT) after a 12-h fast, The insulin level were analyzed at baseline and at 60 and 120 min after glucose loading.

  11. HOMA IR Score at Week 14

    Time frame: Week 14 after intervention

    Insulin resistance was calculated using the homeostatic model assessment (HOMA) index: glucose * insulin / 22.5.

  12. Adiponectin at Week 14

    Time frame: Week 14 after intervention

    Total adiponectin was measured using an RIA kit with an interassay CV of 6.9-9.3% and an intra-assay CV of 1.8-6.2% (Millipore).

  13. Leptin at Week 14

    Time frame: Week 14 after intervention

    Leptin levels were measured using ELISA with an interassay CV of 2.6% to 6.2% and in intra-assay CV of 2.6% to 4.6% (Millipore, Billerica, MA, USA).

  14. C-reactive Protein (CRP) at Week 14

    Time frame: Week 14 after intervention

    High-sensitivity C-reactive protein (Alpco Diagnostics) was measured using a high-sensitivity sandwich ELISA with an intra-assay CV of 5.6%

  15. Insomnia Severity Index (ISI) at Week 14

    Time frame: Week 14 after intervention

    ISI is comprised of 7 items assesses a participant's perception of insomnia. Each item is rated on a 5-point scale from 0 (none) to 4 (very severe). Scores from the questions are summed to assign a total score ranging from 0 to 28, where higher score represents worse insomnia problem.

Sponsors and collaborators

Lead sponsor

Boston University

Other

Registry information

Official study title

Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome

Acronym: TAP

Important dates

Study start
2006
Primary completion
2012
Study completion
2012
First posted
Jul 13, 2006
Registry last updated
Jun 28, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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