Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

NCT ID: NCT00351819

Last Updated: 2017-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2012-11-30

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.

Conditions

Pain; Hypogonadism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Androgel (testosterone gel)

Testosterone replacement therapy

Group Type: ACTIVE_COMPARATOR

AndroGel

Intervention Type: DRUG

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

Placebo

Placebo gel

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

AndroGel

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

testosterone gel

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Boston University

OTHER

Sponsor Role: lead

Responsible Party

Shehzad Basaria

ASSOCIATE PROFESSOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shehzad Basaria, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28981994 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27992261 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25599449 (View on PubMed)

Other Identifiers

H-27995

Identifier Type: -

Identifier Source: org_study_id