Hypogonadism, Male, Opioid Use, Pain
Conditions
Keywords
Pain, Opioid Analgesics, Testosterone
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).
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.
Interventions
DRUGTestosterone Undecanoate 250 MG/ML
Intramuscular administration at a dose of 750 mg at baseline, weeks 4, and week 14.
DRUGPlacebo
Intramuscular administration of placebo at baseline, weeks 4, and week 14.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in scores in the Pain Interference Subscale of the Brief Pain Inventory (BPI) questionnaire | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in response to quantitative sensory testing of pain under pressure stimulus | Baseline, 3 months, and 6 months | 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 | Baseline, 3 months, and 6 months | 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 | 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. |
| Changes in response to quantitative sensory testing of pain under heat stimulus | 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. |
| Changes in response to quantitative sensory testing of pain under cold stimulus | 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. |
| Changes in default mode network connectivity | 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. |
Countries
United States
Contacts
CONTACTJulia Crosby
PRINCIPAL_INVESTIGATORShehzad Basaria, MD
Brigham and Women's Hospital
PRINCIPAL_INVESTIGATORRobert R Edwards, PhD
Brigham and Women's Hospital
Outcome results
None listed