Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

NCT00351819 | Completed Phase 2 Results FDA Drug

• 1 other identifier: H-27995
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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

Conditions

Pain; Hypogonadism

Keywords

Testosterone; Pain; Opioid; Hypogonadism

Outcome Measures

Primary Outcomes (4)

• Brief Pain Inventory (BPI) at Week 14

  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).

  Week14 after intervention

• Algometer-induced Pressure Pain at Week 14

  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.

  Week 14 after intervention

• Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14

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

  Week 14 after intervention

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

  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.

  Week 14 after intervention

Secondary Outcomes (3)

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

  Week14 after intervention

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

  Week 14 after intervention

• Pain Catastrophizing Scale (PCS) at Week 14

  Values at week 14 after intervention

Other Outcomes (15)

• Total Testosterone Values at Week 14

  Week 14 after intervention

• Free Testosterone Values at Week 14

  Week 14 after intervention

• Sex Hormone Binding Globulin (SHBG) at Week 14

  Week 14 after intervention

Study Arms (2)

Androgel (testosterone gel)

ACTIVE COMPARATOR

Testosterone replacement therapy

Drug: AndroGel

Placebo

PLACEBO COMPARATOR

Placebo gel

Other: Placebo

Interventions

AndroGel DRUG

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

Also known as: testosterone gel

Androgel (testosterone gel)

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston University: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• 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.

  PMID: 28981994 DERIVED

• 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.

  PMID: 27992261 DERIVED

• 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.

  PMID: 25599449 DERIVED

MeSH Terms

Conditions

Pain; Hypogonadism

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Shehzad Basaria
• Organization: Brigham and Women's Hospital

sbasaria@partners.org

617-525-9150

Study Officials

• Shehzad Basaria, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Study Record Dates

• First Submitted: July 12, 2006
• First Posted: July 13, 2006
• Study Start: April 1, 2006
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: June 28, 2017
• Results First Posted: June 28, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)