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Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism (PATH)

Primary Purpose

Opioid Use, Pain, Hypogonadism, Male

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Testosterone Undecanoate 250 MG/ML
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use focused on measuring Pain, Opioid Analgesics, Testosterone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Men, age 18 years and older.
  • Chronic non-cancer back 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.

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Testosterone

Placebo

Arm Description

Intramuscular injections of testosterone undecanoate 750 mg.

Intramuscular injections of placebo.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 10, 2021
Last Updated
August 2, 2023
Sponsor
Brigham and Women's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04798469
Brief Title
Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism
Acronym
PATH
Official Title
Androgen Replacement to Improve Patient-Important Outcomes in Men With Opioid-Induced Hypogonadism
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 10, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 back pain treated with opioids who have opioid-induced hypogonadism (low testosterone).
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 back pain who are taking opioid analgesics for at least 6 months and have opioid-induced hypogonadism.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use, Pain, Hypogonadism, Male
Keywords
Pain, Opioid Analgesics, Testosterone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Testosterone
Arm Type
Experimental
Arm Description
Intramuscular injections of testosterone undecanoate 750 mg.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intramuscular injections of placebo.
Intervention Type
Drug
Intervention Name(s)
Testosterone Undecanoate 250 MG/ML
Other Intervention Name(s)
Testosterone
Intervention Description
Intramuscular administration at a dose of 750 mg at baseline, weeks 4, and week 14.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
Intramuscular administration of placebo at baseline, weeks 4, and week 14.
Primary Outcome Measure Information:
Title
Changes in scores in the Pain Interference Subscale of the Brief Pain Inventory (BPI) questionnaire
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Secondary Outcome Measure Information:
Title
Changes in response to quantitative sensory testing of pain under pressure stimulus
Description
Responses to pressure stimulation (pressure pain threshold) will be evaluated using a digital pressure algometer.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in response to quantitative sensory testing of pain under deep pressure stimulus
Description
Response to deep pressure pain will be ascertained using cuff pressure algometry.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in response to quantitative sensory testing of pain under a mechanical stimulus
Description
Responses to mechanical pain will be assessed using repetitive stimuli (temporal summation or "windup") with a set of punctate mechanical probes.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in response to quantitative sensory testing of pain under heat stimulus
Description
Responses to heat pain will be assessed using a contact thermode that will deliver thermal stimulation to the skin.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in response to quantitative sensory testing of pain under cold stimulus
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in default mode network connectivity
Description
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.
Time Frame
Baseline and 6 months
Other Pre-specified Outcome Measures:
Title
Changes in quality of life assessed using the 36-Item Short-Form Survey (SF-36)
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9)
Description
The PHQ-9 is a validated health questionnaire that will be administered in this trial to evaluate depression among the participants.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in mood and well-being, assessed using the by Positive and Negative Affect Scale (PANAS) affectivity balance scale
Description
The PANAS affectivity balance scale includes 10 questions evaluating positive and negative affect.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in energy, assessed with the Hypogonadism Energy Diary (HED)
Description
The HED questionnaire is a self-administered instrument that evaluates energy levels in men with hypogonadism.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in sexual function, assessed with the Sexual Arousal, Interest, and Drive (SAID) questionnaire
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in fatigue assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire
Description
The FACIT-F questionnaire is a self-reported instrument that evaluates fatigue and its impact on daily activities and function.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in catastrophizing assessed with the Pain Catastrophizing Scale (PCS) questionnaire
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Title
Changes in Patient's Global Impression of Change (PGIC) scores
Description
The PGIC is a questionnaire that asks how subjects feel their health status has changed at the end of the study compared with baseline.
Time Frame
Baseline and 6 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men, age 18 years and older. Chronic non-cancer back 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Leila Chammas
Phone
617-278-0722
Email
lchammas@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shehzad Basaria, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert R Edwards, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leila Chammas
Phone
617-278-0722
Email
lchammas@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Shehzad Basaria, MD
First Name & Middle Initial & Last Name & Degree
Robert R Edwards, PhD
First Name & Middle Initial & Last Name & Degree
Vitaly Napadow, PhD
First Name & Middle Initial & Last Name & Degree
Thomas G Travison, PhD
First Name & Middle Initial & Last Name & Degree
Grace Huang, MD

12. IPD Sharing Statement

Plan to Share IPD
No
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Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism

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