Clinical trial NCT00351819: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception
Official title: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pain
Hypogonadism
Keywords: Testosterone
Pain
Opioid
Hypogonadism
Lead sponsor: Boston University
Sponsor class: OTHER
First posted: 2006-07-13
Enrollment: 84
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Brief Pain Inventory (BPI) at Week 14
timeFrame: Week14 after intervention
measure: Algometer-induced Pressure Pain at Week 14
timeFrame: Week 14 after intervention
measure: Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14
timeFrame: Week 14 after intervention
measure: Ice Water-induced Cold Pain and Its After-sensation at Week 14
timeFrame: Week 14 after intervention
Secondary outcomes:
measure: Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14
timeFrame: Week14 after intervention
measure: Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14
timeFrame: Week 14 after intervention
measure: Pain Catastrophizing Scale (PCS) at Week 14
timeFrame: Values at week 14 after intervention
Other outcomes:
measure: Total Testosterone Values at Week 14
timeFrame: Week 14 after intervention
measure: Free Testosterone Values at Week 14
timeFrame: Week 14 after intervention
measure: Sex Hormone Binding Globulin (SHBG) at Week 14
timeFrame: Week 14 after intervention
measure: Luteinizing Hormone Values at Week 14
timeFrame: Week 14 after intervention
measure: Inflammatory Cytokines at Week 14
timeFrame: Week 14 after intervention
measure: Body Composition at Week 14
timeFrame: Week 14 after intervention
measure: Lipid Profile at Week 14
timeFrame: Week 14 after intervention
measure: HbA1c at Week 14
timeFrame: Week 14 after intervention
measure: Glucose Level in Oral Glucose Tolerance Test (OGTT) at Week 14
timeFrame: Week 14 after intervention
measure: Insulin Level in Oral Glucose Tolerance Test (OGTT) at Week 14
timeFrame: Values at week 14 after intervention
measure: HOMA IR Score at Week 14
timeFrame: Week 14 after intervention
measure: Adiponectin at Week 14
timeFrame: Week 14 after intervention
measure: Leptin at Week 14
timeFrame: Week 14 after intervention
measure: C-reactive Protein (CRP) at Week 14
timeFrame: Week 14 after intervention
measure: Insomnia Severity Index (ISI) at Week 14
timeFrame: Week 14 after intervention
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shehzad Basaria, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhasin S, Travison TG, O'Brien L, MacKrell J, Krishnan V, Ouyang H, Pencina K, Basaria S. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology. 2018 Jan;6(1):151-157. doi: 10.1111/andr.12428. Epub 2017 Oct 5.
citation: Gagliano-Juca T, Icli TB, Pencina KM, Li Z, Tapper J, Huang G, Travison TG, Tsitouras P, Harman SM, Storer TW, Bhasin S, Basaria S. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials. J Clin Endocrinol Metab. 2017 May 1;102(5):1478-1485. doi: 10.1210/jc.2016-3669.
citation: Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, Eder R, Lakshman K, Bachman E, Mensing G, Martel MO, Le D, Stroh H, Bhasin S, Wasan AD, Edwards RR. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015 Feb;156(2):280-288. doi: 10.1097/01.j.pain.0000460308.86819.aa.