Opioid UsePhase 2PATHNCT04798469
Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism
A Phase 2 study testing Testosterone Undecanoate 250 MG/ML in people with Opioid Use and Pain, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Opioid Use, Pain, Hypogonadism, Male
- What is being tested?
- Testosterone Undecanoate 250 MG/ML
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2022to 30 Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Julia Crosby, 617-525-6726, jpcrosby@bwh.harvard.edu
Shehzad Basaria, MD
About this study
Official title: Androgen Replacement to Improve Patient-Important Outcomes in Men With Opioid-Induced Hypogonadism
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).
Read the detailed description
This single-center, randomized, double-blind, placebo-controlled, parallel-group trial will evaluate pain and quality of life outcomes associated with 6 months of treatment with testosterone or placebo in men aged 18 years or older with chronic non-cancer spinal pain who are taking opioid analgesics for at least 6 months and have opioid-induced hypogonadism.
- Conditions
- Opioid Use, Pain, Hypogonadism, Male
- Being tested
- Testosterone Undecanoate 250 MG/ML, Placebo
- Keywords
- Pain, Opioid Analgesics, Testosterone
- Medical subject headings
- Pain, Eunuchism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Testosterone Undecanoate 250 MG/MLDrug
Also called Testosterone
Intramuscular administration at a dose of 750 mg at baseline, weeks 4, and week 14.
PlaceboDrug
Also called Control
Intramuscular administration of placebo at baseline, weeks 4, and week 14.
| Study group | Role | What they receive |
|---|---|---|
| Testosterone | Experimental | Intramuscular injections of testosterone undecanoate 750 mg. Receives: Drug: Testosterone Undecanoate 250 MG/ML |
| Placebo | Placebo comparator | Intramuscular injections of placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 3 months, and 6 months
Secondary outcomes (6)
Changes in response to quantitative sensory testing of pain under pressure stimulus
Responses to pressure stimulation (pressure pain threshold) will be evaluated using a digital pressure algometer.
Measured: Baseline, 3 months, and 6 months
Changes in response to quantitative sensory testing of pain under deep pressure stimulus
Response to deep pressure pain will be ascertained using cuff pressure algometry.
Measured: Baseline, 3 months, and 6 months
Changes in response to quantitative sensory testing of pain under a mechanical stimulus
Responses to mechanical pain will be assessed using repetitive stimuli (temporal summation or "windup") with a set of punctate mechanical probes.
Measured: Baseline, 3 months, and 6 months
Changes in response to quantitative sensory testing of pain under heat stimulus
Responses to heat pain will be assessed using a contact thermode that will deliver thermal stimulation to the skin.
Measured: Baseline, 3 months, and 6 months
Changes in response to quantitative sensory testing of pain under cold stimulus
Responses to cold pain will be assessed using a cold pressor task, which involves immersion of the dominant hand in a circulating water bath at a temperature of 4°C.
Measured: Baseline, 3 months, and 6 months
Changes in default mode network connectivity
Patients with chronic pain show increased default mode network (DMN) connectivity to the anterior/mid-insula, a brain region that integrates multiple dimensions of pain, while reduced DMN connectivity to the insula has been significantly associated with pain reduction. In this trial, we plan to determine the influence of testosterone replacement on DMN connectivity by performing functional magnetic resonance imaging (MRI) before and after testosterone/placebo administration and correlate changes in pain with changes in DMN connectivity.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start10 Jan 2022
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Opioid UseStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shehzad Basaria, M.D., Brigham and Women's Hospital
- Investigators
- Shehzad Basaria, MD, Principal investigator, Brigham and Women's HospitalRobert R Edwards, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04798469
- Sponsor's protocol ID
- 2021P000331
- Acronym
- PATH
- Status last verified
- Jul 2026
- First submitted
- 10 Mar 2021
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25581257Von 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.
PubMed 21893626Aloisi 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.
PubMed 14993056Fillingim 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.
PubMed 10568849Basaria S. Male hypogonadism. Lancet. 2014 Apr 5;383(9924):1250-63. doi: 10.1016/S0140-6736(13)61126-5. Epub 2013 Oct 10.
PubMed 24119423Fillingim 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.
PubMed 11323144Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002 Oct;3(5):377-84. doi: 10.1054/jpai.2002.126790.
PubMed 14622741Rajagopal 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.
PubMed 14770444Basaria 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.
PubMed 25599449Huang 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.
PubMed 27550959Kregel 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.
PubMed 26092329Meints 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.
PubMed 30531308Katz 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.
PubMed 19333165Edwards 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.
PubMed 26933094Frye 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.
PubMed 12467088