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NCT Number: NCT04798469

Pain Alleviation With Testosterone in 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).

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Key information

Conditions

Opioid Use Endocrine System Diseases Eunuchism Gonadal Disorders Hypogonadism Hypogonadism, Male Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location status: Recruiting

Location contact

Julia Crosby

CONTACT

[email protected]

617-525-6726

Robert R Edwards, PhD

PRINCIPAL_INVESTIGATOR

Shehzad Basaria, MD

PRINCIPAL_INVESTIGATOR

Thomas G Travison, PhD

SUB_INVESTIGATOR

Vitaly Napadow, PhD

SUB_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Testosterone Undecanoate 250 MG/ML

Drug

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

Other names: Testosterone

Placebo

Drug

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

Other names: Control

Primary outcomes

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

    Time frame: Baseline, 3 months, and 6 months

    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.

Secondary outcomes

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

    Time frame: Baseline, 3 months, and 6 months

    Responses to pressure stimulation (pressure pain threshold) will be evaluated using a digital pressure algometer.

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

    Time frame: Baseline, 3 months, and 6 months

    Response to deep pressure pain will be ascertained using cuff pressure algometry.

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

    Time frame: Baseline, 3 months, and 6 months

    Responses to mechanical pain will be assessed using repetitive stimuli (temporal summation or "windup") with a set of punctate mechanical probes.

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

    Time frame: Baseline, 3 months, and 6 months

    Responses to heat pain will be assessed using a contact thermode that will deliver thermal stimulation to the skin.

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

    Time frame: Baseline, 3 months, and 6 months

    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.

  6. Changes in default mode network connectivity

    Time frame: Baseline and 6 months

    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.

Other outcomes

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

    Time frame: Baseline, 3 months, and 6 months

    The SF-36 measures eight QOL domains: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. The questionnaire also includes a single item that provides an indication of perceived change in health.

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

    Time frame: Baseline, 3 months, and 6 months

    The PHQ-9 is a validated health questionnaire that will be administered in this trial to evaluate depression among the participants.

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

    Time frame: Baseline, 3 months, and 6 months

    The PANAS affectivity balance scale includes 10 questions evaluating positive and negative affect.

  4. Changes in energy, assessed with the Hypogonadism Energy Diary (HED)

    Time frame: Baseline, 3 months, and 6 months

    The HED questionnaire is a self-administered instrument that evaluates energy levels in men with hypogonadism.

  5. Changes in sexual function, assessed with the Sexual Arousal, Interest, and Drive (SAID) questionnaire

    Time frame: Baseline, 3 months, and 6 months

    The SAID questionnaire is a five-item self-administered instrument that evaluates the level of thinking about sex, arousal, and rating the level of interest in sex and sex drive in men with hypogonadism.

  6. Changes in fatigue assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire

    Time frame: Baseline, 3 months, and 6 months

    The FACIT-F questionnaire is a self-reported instrument that evaluates fatigue and its impact on daily activities and function.

  7. Changes in catastrophizing assessed with the Pain Catastrophizing Scale (PCS) questionnaire

    Time frame: Baseline, 3 months, and 6 months

    The PCS is a measure of cognitive and affective responses to pain that consists of 13 items assessing the pain catastrophizing domains of rumination, magnification, and helplessness.

  8. Changes in Patient's Global Impression of Change (PGIC) scores

    Time frame: Baseline and 6 months

    The PGIC is a questionnaire that asks how subjects feel their health status has changed at the end of the study compared with baseline.

Study contacts

Contact information is provided by the study sponsor or research team.

Julia Crosby

CONTACT

[email protected]

617-525-6726

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Registry information

Official study title

Androgen Replacement to Improve Patient-Important Outcomes in Men With Opioid-Induced Hypogonadism

Acronym: PATH

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Mar 15, 2021
Registry last updated
Jul 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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