AzTrials
AzTrials

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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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
Are there results?
Not yet: the study is under way

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.
Show all 12Show fewer
  • 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.

Julia Crosby contact

617-525-6726

jpcrosby@bwh.harvard.edu

United States1 site, 1 recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Julia Crosby, 617-525-6726, jpcrosby@bwh.harvard.edu

    Shehzad Basaria, MD

    Recruiting

Other trials in United States

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.

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 groups in NCT04798469
Study groupRoleWhat they receive
TestosteroneExperimentalIntramuscular injections of testosterone undecanoate 750 mg.
Receives: Drug: Testosterone Undecanoate 250 MG/ML
PlaceboPlacebo comparatorIntramuscular injections of placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, 3 months, and 6 months

Secondary outcomes (6)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  1. First posted15 Mar 2021
  2. Study start10 Jan 2022
  3. Primary completion30 Sep 2027 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

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)
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 25581257

  • 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.

    PubMed 21893626

  • 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.

    PubMed 14993056

  • 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.

    PubMed 10568849

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

    PubMed 24119423

  • 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.

    PubMed 11323144

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

    PubMed 14622741

  • 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.

    PubMed 14770444

  • 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.

    PubMed 25599449

  • 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.

    PubMed 27550959

  • 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.

    PubMed 26092329

  • 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.

    PubMed 30531308

  • 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.

    PubMed 19333165

  • 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.

    PubMed 26933094

  • 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.

    PubMed 12467088

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Julia Crosby (617-525-6726, jpcrosby@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in scores in the Pain Interference Subscale of the Brief Pain Inventory (BPI) questionnaire (time frame: Baseline, 3 months, and 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04798469, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in