Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism

NCT04798469 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2021P000331
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, fatigue, and quality of life when compared with placebo in men with chronic spinal pain treated with opioids who have opioid-induced hypogonadism (low testosterone).

Conditions

Opioid Use; Pain; Hypogonadism, Male

Keywords

Pain; Opioid Analgesics; Testosterone

Outcome Measures

Primary Outcomes (1)

• Changes in scores in the Pain Interference Subscale of the Brief Pain Inventory (BPI) questionnaire

  The Pain Interference Subscale of the BPI is specifically relevant to patients with chronic back pain who are using opioids and correlates strongly with the patient's quality of life.

  Baseline, 3 months, and 6 months

Secondary Outcomes (6)

• Changes in response to quantitative sensory testing of pain under pressure stimulus

  Baseline, 3 months, and 6 months

• Changes in response to quantitative sensory testing of pain under deep pressure stimulus

  Baseline, 3 months, and 6 months

• Changes in response to quantitative sensory testing of pain under a mechanical stimulus

  Baseline, 3 months, and 6 months

• Changes in response to quantitative sensory testing of pain under heat stimulus

  Baseline, 3 months, and 6 months

• Changes in response to quantitative sensory testing of pain under cold stimulus

  Baseline, 3 months, and 6 months

Other Outcomes (8)

• Changes in quality of life assessed using the 36-Item Short-Form Survey (SF-36)

  Baseline, 3 months, and 6 months

• Changes in depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9)

  Baseline, 3 months, and 6 months

• Changes in mood and well-being, assessed using the by Positive and Negative Affect Scale (PANAS) affectivity balance scale

  Baseline, 3 months, and 6 months

Study Arms (2)

Testosterone

EXPERIMENTAL

Intramuscular injections of testosterone undecanoate 750 mg.

Drug: Testosterone Undecanoate 250 MG/ML

Placebo

PLACEBO COMPARATOR

Intramuscular injections of placebo.

Drug: Placebo

Interventions

Testosterone Undecanoate 250 MG/ML DRUG

Intramuscular administration at a dose of 750 mg at baseline, weeks 4, and week 14.

Also known as: Testosterone

Testosterone

Placebo DRUG

Intramuscular administration of placebo at baseline, weeks 4, and week 14.

Also known as: Control

Placebo

Eligibility Criteria

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

You may qualify if:

• Men, age 18 years and older.
• Chronic non-cancer spinal pain.
• Use of opioid analgesics for at least 6 months.
• Serum total testosterone (measured by mass spectrometry) \<348 ng/dL and/or free testosterone \<70 pg/mL.
• Ability and willingness to provide informed consent.

You may not qualify if:

• History of prostate cancer or breast cancer.
• Known history of organic hypogonadism (e.g., due to hypothalamic, pituitary or testicular disease).
• Use of testosterone within the past 6 months.
• Baseline hematocrit \>48%.
• Prostate-specific antigen (PSA) level \>4 ng/mL in Caucasians or \>3 ng/mL in African-Americans.
• Presence of prostate nodule or induration on digital rectal examination.
• Uncontrolled congestive heart failure.
• Myocardial infarction, acute coronary syndrome, revascularization surgery or stroke within 3 months.
• Serum creatinine \>2.5 mg/dL.
• Alanine aminotransferase (ALT) level 3 times above the upper limit of normal.
• Diagnosis of bipolar disorder or schizophrenia.
• Presence of metallic implants (pacemakers, aneurysm clips, etc.) that preclude the patient from undergoing functional magnetic resonance imaging (MRI). In subjects who are otherwise eligible and either do not qualify for MRI or are reluctant to undergo imaging, the investigators may consider enrolling such participants on a case-by-case basis.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (18)

• Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Feb 17;162(4):276-86. doi: 10.7326/M14-2559.

  PMID: 25581257 BACKGROUND

• Von Korff M, Kolodny A, Deyo RA, Chou R. Long-term opioid therapy reconsidered. Ann Intern Med. 2011 Sep 6;155(5):325-8. doi: 10.7326/0003-4819-155-5-201109060-00011.

  PMID: 21893626 BACKGROUND

• Aloisi AM, Ceccarelli I, Fiorenzani P. Gonadectomy affects hormonal and behavioral responses to repetitive nociceptive stimulation in male rats. Ann N Y Acad Sci. 2003 Dec;1007:232-7. doi: 10.1196/annals.1286.022.

  PMID: 14993056 BACKGROUND

• Fillingim RB, Edwards RR, Powell T. The relationship of sex and clinical pain to experimental pain responses. Pain. 1999 Dec;83(3):419-425. doi: 10.1016/S0304-3959(99)00128-1.

  PMID: 10568849 BACKGROUND

• Basaria S. Male hypogonadism. Lancet. 2014 Apr 5;383(9924):1250-63. doi: 10.1016/S0140-6736(13)61126-5. Epub 2013 Oct 10.

  PMID: 24119423 BACKGROUND

• Fillingim RB, Edwards RR. The association of hormone replacement therapy with experimental pain responses in postmenopausal women. Pain. 2001 May;92(1-2):229-34. doi: 10.1016/s0304-3959(01)00256-1.

  PMID: 11323144 BACKGROUND

• Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002 Oct;3(5):377-84. doi: 10.1054/jpai.2002.126790.

  PMID: 14622741 BACKGROUND

• Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, Kaur G, Bruera E. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer. 2004 Feb 15;100(4):851-8. doi: 10.1002/cncr.20028.

  PMID: 14770444 BACKGROUND

• 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 BACKGROUND

• Huang G, Travison TG, Edwards RR, Basaria S. Effects of Testosterone Replacement on Pain Catastrophizing and Sleep Quality in Men with Opioid-Induced Androgen Deficiency. Pain Med. 2017 Jun 1;18(6):1070-1076. doi: 10.1093/pm/pnw159.

  PMID: 27550959 BACKGROUND

• Kregel J, Meeus M, Malfliet A, Dolphens M, Danneels L, Nijs J, Cagnie B. Structural and functional brain abnormalities in chronic low back pain: A systematic review. Semin Arthritis Rheum. 2015 Oct;45(2):229-37. doi: 10.1016/j.semarthrit.2015.05.002. Epub 2015 May 16.

  PMID: 26092329 BACKGROUND

• Meints SM, Mawla I, Napadow V, Kong J, Gerber J, Chan ST, Wasan AD, Kaptchuk TJ, McDonnell C, Carriere J, Rosen B, Gollub RL, Edwards RR. The relationship between catastrophizing and altered pain sensitivity in patients with chronic low-back pain. Pain. 2019 Apr;160(4):833-843. doi: 10.1097/j.pain.0000000000001461.

  PMID: 30531308 BACKGROUND

• Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009 Feb;25(2):170-5. doi: 10.1097/AJP.0b013e3181850df6.

  PMID: 19333165 BACKGROUND

• Edwards RR, Dolman AJ, Michna E, Katz JN, Nedeljkovic SS, Janfaza D, Isaac Z, Martel MO, Jamison RN, Wasan AD. Changes in Pain Sensitivity and Pain Modulation During Oral Opioid Treatment: The Impact of Negative Affect. Pain Med. 2016 Oct;17(10):1882-1891. doi: 10.1093/pm/pnw010. Epub 2016 Mar 1.

  PMID: 26933094 BACKGROUND

• Frye CA, Seliga AM. Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats. Cogn Affect Behav Neurosci. 2001 Dec;1(4):371-81. doi: 10.3758/cabn.1.4.371.

  PMID: 12467088 BACKGROUND

• Forman LJ, Tingle V, Estilow S, Cater J. The response to analgesia testing is affected by gonadal steroids in the rat. Life Sci. 1989;45(5):447-54. doi: 10.1016/0024-3205(89)90631-0.

  PMID: 2770410 BACKGROUND

• Daniell HW, Lentz R, Mazer NA. Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency. J Pain. 2006 Mar;7(3):200-10. doi: 10.1016/j.jpain.2005.10.009.

  PMID: 16516826 BACKGROUND

• Aloisi AM, Ceccarelli I, Carlucci M, Suman A, Sindaco G, Mameli S, Paci V, Ravaioli L, Passavanti G, Bachiocco V, Pari G. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol. 2011 Feb 18;9:26. doi: 10.1186/1477-7827-9-26.

  PMID: 21332999 BACKGROUND

MeSH Terms

Conditions

Pain; Eunuchism

Interventions

testosterone undecanoate; Testosterone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hypogonadism; 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

Study Officials

• Shehzad Basaria, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Robert R Edwards, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Crosby

CONTACT

617-525-6726; jpcrosby@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Harvard Medical School; Associate Director, Section on Men's Health, Aging & Metabolism, Brigham and Women's Hospital

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 15, 2021
• Study Start: January 10, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)