Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception (TAP)
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.
Testosterone replacement in men with opioid-induced hypogonadism will improve pain tolerance, pain perception and quality of life.
- To evaluate the effects of testosterone replacement on pain sensitivity, pain tolerance, and pain modulation in men with opioid-induced hypogonadism.
- To determine the effects of testosterone replacement on health-related quality of life.
- 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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
|Official Title:||Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome|
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Free Testosterone Values at Week 14 [ Time Frame: Week 14 after intervention ]Free testosterone was calculated using a law of mass action equation.
- 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.
- 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.
- 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).
- Body Composition at Week 14 [ Time Frame: Week 14 after intervention ]Body composition was measured using dual-energy X-ray absorptiometry scan.
- 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.
- HbA1c at Week 14 [ Time Frame: Week 14 after intervention ]
- 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.
- 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.
- 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.
- 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).
- 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).
- 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%
- 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.
|Study Start Date:||April 2006|
|Study Completion Date:||November 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Androgel (testosterone gel)
Testosterone replacement therapy
5g gel, applied once daily to the upper arms, upper back or shoulders.
Other Name: testosterone gel
Placebo Comparator: Placebo
5g gel, applied once daily to the upper arms, upper back or shoulders.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00351819
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Shehzad Basaria, MD||Brigham and Women's Hospital|