Ignite Creation Date:
2025-12-24 @ 11:06 PM
Ignite Modification Date:
2025-12-25 @ 8:38 PM
Study NCT ID:
NCT04798469
Status:
RECRUITING
Last Update Posted:
2025-06-19
First Post:
2021-03-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010146', 'term': 'Pain'}, {'id': 'D005058', 'term': 'Eunuchism'}], 'ancestors': [{'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D007006', 'term': 'Hypogonadism'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C010792', 'term': 'testosterone undecanoate'}, {'id': 'D013739', 'term': 'Testosterone'}], 'ancestors': [{'id': 'D000737', 'term': 'Androstenols'}, {'id': 'D000736', 'term': 'Androstenes'}, {'id': 'D000731', 'term': 'Androstanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D045165', 'term': 'Testosterone Congeners'}, {'id': 'D012739', 'term': 'Gonadal Steroid Hormones'}, {'id': 'D042341', 'term': 'Gonadal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 150}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-01-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-17', 'studyFirstSubmitDate': '2021-03-10', 'studyFirstSubmitQcDate': '2021-03-12', 'lastUpdatePostDateStruct': {'date': '2025-06-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-03-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-05-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Changes in quality of life assessed using the 36-Item Short-Form Survey (SF-36)', 'timeFrame': 'Baseline, 3 months, and 6 months', '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.'}, {'measure': 'Changes in depressive symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9)', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'The PHQ-9 is a validated health questionnaire that will be administered in this trial to evaluate depression among the participants.'}, {'measure': 'Changes in mood and well-being, assessed using the by Positive and Negative Affect Scale (PANAS) affectivity balance scale', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'The PANAS affectivity balance scale includes 10 questions evaluating positive and negative affect.'}, {'measure': 'Changes in energy, assessed with the Hypogonadism Energy Diary (HED)', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'The HED questionnaire is a self-administered instrument that evaluates energy levels in men with hypogonadism.'}, {'measure': 'Changes in sexual function, assessed with the Sexual Arousal, Interest, and Drive (SAID) questionnaire', 'timeFrame': 'Baseline, 3 months, and 6 months', '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.'}, {'measure': 'Changes in fatigue assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'The FACIT-F questionnaire is a self-reported instrument that evaluates fatigue and its impact on daily activities and function.'}, {'measure': 'Changes in catastrophizing assessed with the Pain Catastrophizing Scale (PCS) questionnaire', 'timeFrame': 'Baseline, 3 months, and 6 months', '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.'}, {'measure': "Changes in Patient's Global Impression of Change (PGIC) scores", 'timeFrame': 'Baseline and 6 months', '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.'}], 'primaryOutcomes': [{'measure': 'Changes in scores in the Pain Interference Subscale of the Brief Pain Inventory (BPI) questionnaire', 'timeFrame': 'Baseline, 3 months, and 6 months', '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."}], 'secondaryOutcomes': [{'measure': 'Changes in response to quantitative sensory testing of pain under pressure stimulus', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'Responses to pressure stimulation (pressure pain threshold) will be evaluated using a digital pressure algometer.'}, {'measure': 'Changes in response to quantitative sensory testing of pain under deep pressure stimulus', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'Response to deep pressure pain will be ascertained using cuff pressure algometry.'}, {'measure': 'Changes in response to quantitative sensory testing of pain under a mechanical stimulus', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'Responses to mechanical pain will be assessed using repetitive stimuli (temporal summation or "windup") with a set of punctate mechanical probes.'}, {'measure': 'Changes in response to quantitative sensory testing of pain under heat stimulus', 'timeFrame': 'Baseline, 3 months, and 6 months', 'description': 'Responses to heat pain will be assessed using a contact thermode that will deliver thermal stimulation to the skin.'}, {'measure': 'Changes in response to quantitative sensory testing of pain under cold stimulus', 'timeFrame': 'Baseline, 3 months, and 6 months', '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.'}, {'measure': 'Changes in default mode network connectivity', 'timeFrame': 'Baseline and 6 months', '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.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Pain', 'Opioid Analgesics', 'Testosterone'], 'conditions': ['Opioid Use', 'Pain', 'Hypogonadism, Male']}, 'referencesModule': {'references': [{'pmid': '25581257', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '21893626', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '14993056', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '10568849', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '24119423', 'type': 'BACKGROUND', 'citation': 'Basaria S. Male hypogonadism. Lancet. 2014 Apr 5;383(9924):1250-63. doi: 10.1016/S0140-6736(13)61126-5. Epub 2013 Oct 10.'}, {'pmid': '11323144', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '14622741', 'type': 'BACKGROUND', 'citation': 'Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002 Oct;3(5):377-84. doi: 10.1054/jpai.2002.126790.'}, {'pmid': '14770444', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '25599449', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '27550959', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '26092329', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '30531308', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '19333165', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '26933094', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '12467088', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '2770410', 'type': 'BACKGROUND', 'citation': 'Forman LJ, Tingle V, Estilow S, Cater J. The response to analgesia testing is affected by gonadal steroids in the rat. Life Sci. 1989;45(5):447-54. doi: 10.1016/0024-3205(89)90631-0.'}, {'pmid': '16516826', 'type': 'BACKGROUND', 'citation': 'Daniell HW, Lentz R, Mazer NA. Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency. J Pain. 2006 Mar;7(3):200-10. doi: 10.1016/j.jpain.2005.10.009.'}, {'pmid': '21332999', 'type': 'BACKGROUND', 'citation': 'Aloisi AM, Ceccarelli I, Carlucci M, Suman A, Sindaco G, Mameli S, Paci V, Ravaioli L, Passavanti G, Bachiocco V, Pari G. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol. 2011 Feb 18;9:26. doi: 10.1186/1477-7827-9-26.'}]}, 'descriptionModule': {'briefSummary': '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).', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Men, age 18 years and older.\n* Chronic non-cancer spinal pain.\n* Use of opioid analgesics for at least 6 months.\n* Serum total testosterone (measured by mass spectrometry) \\<348 ng/dL and/or free testosterone \\<70 pg/mL.\n* Ability and willingness to provide informed consent.\n\nExclusion Criteria:\n\n* History of prostate cancer or breast cancer.\n* Known history of organic hypogonadism (e.g., due to hypothalamic, pituitary or testicular disease).\n* Use of testosterone within the past 6 months.\n* Baseline hematocrit \\>48%.\n* Prostate-specific antigen (PSA) level \\>4 ng/mL in Caucasians or \\>3 ng/mL in African-Americans.\n* Presence of prostate nodule or induration on digital rectal examination.\n* Uncontrolled congestive heart failure.\n* Myocardial infarction, acute coronary syndrome, revascularization surgery or stroke within 3 months.\n* Serum creatinine \\>2.5 mg/dL.\n* Alanine aminotransferase (ALT) level 3 times above the upper limit of normal.\n* Diagnosis of bipolar disorder or schizophrenia.\n* 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.'}, 'identificationModule': {'nctId': 'NCT04798469', 'acronym': 'PATH', 'briefTitle': 'Pain Alleviation With Testosterone in Opioid-Induced Hypogonadism', 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': 'Androgen Replacement to Improve Patient-Important Outcomes in Men With Opioid-Induced Hypogonadism', 'orgStudyIdInfo': {'id': '2021P000331'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Testosterone', 'description': 'Intramuscular injections of testosterone undecanoate 750 mg.', 'interventionNames': ['Drug: Testosterone Undecanoate 250 MG/ML']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Intramuscular injections of placebo.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Testosterone Undecanoate 250 MG/ML', 'type': 'DRUG', 'otherNames': ['Testosterone'], 'description': 'Intramuscular administration at a dose of 750 mg at baseline, weeks 4, and week 14.', 'armGroupLabels': ['Testosterone']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Control'], 'description': 'Intramuscular administration of placebo at baseline, weeks 4, and week 14.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Leila Chammas', 'role': 'CONTACT', 'email': 'lchammas@bwh.harvard.edu', 'phone': '617-278-0722'}, {'name': 'Shehzad Basaria, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Robert R Edwards, PhD', 'role': 'PRINCIPAL_INVESTIGATOR'}, {'name': 'Vitaly Napadow, PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Thomas G Travison, PhD', 'role': 'SUB_INVESTIGATOR'}], 'facility': "Brigham and Women's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'centralContacts': [{'name': 'Joseph Badros', 'role': 'CONTACT', 'email': 'jbadros@bwh.harvard.edu', 'phone': '617-278-0722'}], 'overallOfficials': [{'name': 'Shehzad Basaria, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}, {'name': 'Robert R Edwards, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': "Professor of Medicine, Harvard Medical School; Associate Director, Section on Men's Health, Aging & Metabolism, Brigham and Women's Hospital", 'investigatorFullName': 'Shehzad Basaria, M.D.', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}