Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

NCT03482479 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: VCRC5564
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 7

Brief Summary

Naltrexone is an FDA approved drug (for alcoholism) that has found widespread use "off-label" to treat pain and improve quality of life at much lower doses than are used for the approved indication. There are a few scientific studies in three conditions (fibromyalgia, Crohn's disease, and multiple sclerosis) that suggest that this drug has benefit and is safe. However, considering the extent of use in other conditions, and uncertainty about the mechanism of action study is needed in a diverse set of diseases, including vasculitis. The purpose of this clinical trial is to determine if low dose naltrexone is effective in improving health-related quality of life (HRQoL) among patients with vasculitis. Although it is a pilot study, a placebo-controlled component is used because of the prominent placebo group effect seen in studies with self-reported subjective outcomes.

Conditions

Churg-Strauss Syndrome (CSS); Giant Cell Arteritis; Granulomatosis With Polyangiitis; Microscopic Polyangiitis; Eosinophilic Granulomatosis With Polyangiitis (EGPA); Polyarteritis Nodosa; Takayasu Arteritis

Outcome Measures

Primary Outcomes (1)

• PROMIS Global Physical Health

  Questionnaire about improved health related quality of life to a greater extent than placebo.

  Week 12.

Secondary Outcomes (5)

• PROMIS Global Physical Health

  9 weeks

• SF-36 (physical component subscore)

  12 weeks

• PROMIS Questionnaires

  12 weeks

• Clinical Global Impression of Severity (CGI-S)

  12 weeks

• Clinical Global Impression of Improvement (CGI-I)

  12 weeks

Study Arms (2)

Naltrexone Hydrochloride

EXPERIMENTAL

Naltrexone hydrochloride for oral use, 4.5 mg per capsule, taken once a day for 6 weeks.

Other: Placebo Comparator

Placebo Comparator

PLACEBO COMPARATOR

Placebo to match naltrexone for oral use to be taken once a day for 6 weeks.

Drug: Naltrexone Hydrochloride

Interventions

Naltrexone Hydrochloride DRUG

Naltrexone Hydrochloride will be taken daily (dose 4.5 mg) for six weeks

Placebo Comparator

Placebo Comparator OTHER

A placebo tablet which matches the drug will be taken daily for 6 weeks.

Naltrexone Hydrochloride

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria in order to be eligible for enrollment:
• \. Criteria for diagnosis of giant cell arteritis (GCA), Takayasu's arteritis (TAK), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA, Wegener's), microscopic polyangiitis (MPA), or eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss), as used for the VCRC longitudinal studies
• a. Giant cell arteritis: According to the American College of Rheumatology (ACR) criteria for classification of GCA, meeting at least 2 of the following 5 remaining criteria at the time of diagnosis of GCA: Age of disease onset \>50 years (required) i. New onset or new type of localized pain in the head ii. Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries) iii. ESR of \>40 mm in the first hour by Westergren method iv. Temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells v. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else
• i. Major criteria (not explained by other causes):
• Arteriographic abnormality
• Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
• Mononeuropathy or polyneuropathy ii. Minor criteria (not explained by other causes)
• \. Weight loss \> 4 kg 2. Livedo reticularis, cutaneous ulcerations, or skin nodules 3. Testicular pain or tenderness 4. Myalgias 5. Diastolic blood pressure \>90mm Hg 6. Elevated BUN or serum creatinine levels 7. Ischemic abdominal pain iii. Isolated cutaneous polyarteritis nodosa
• Biopsy-proven cutaneous PAN
• d. Granulomatosis with polyangiitis: Participants can be enrolled if two of the five modified American College of Rheumatology criteria are met: i. Nasal or oral inflammation: painful or painless oral ulcers or purulent or blood nasal discharge ii. Abnormal chest radiograph: nodules, fixed infiltrates, or cavities iii. Urinary sediment: microhematuria or red cell casts iv. Granulomatous inflammation on biopsy: granulomatous inflammation within the wall of an artery or in the perivascular area v. ANCA positivity by enzyme immunoassay for either PR3- or MPO-ANCA e. Microscopic polyangiitis: The following Chapel Hill Consensus Conference Definitions for MPA need to be met: i. Necrotizing vasculitis with few or no immune deposits affects small vessel (i.e., capillaries, venules, or arterioles) ii. Necrotizing arteritis involving small and medium-sized arteritis may be present iii. Necrotizing glomerulonephritis is very common iv. Pulmonary capillaritis often occurs
• Baseline normalized score on PROMIS Global Physical Health of 40 or lower.
• Vasculitis in remission or very low disease activity, as defined by Physician Global Assessment 0-1 for at least 12 weeks
• Stable immunosuppressive therapy (including prednisone) related to vasculitis for at least 12 weeks
• No change in medications in the past 12 weeks made with the expectation of improving pain, fatigue, or mood
• No plan to change medication or a non-pharmacologic treatment regimen likely to affect pain, fatigue, mood, or vasculitis activity during the next 12 weeks

You may not qualify if:

• Change in any medication related to control of vasculitis, pain, fatigue, or mood within the past 12 weeks (medications taken as needed must be in a stable pattern per the patient's estimation)
• Use of another investigational agent as part of a clinical trial within 30 days of enrollment
• Current use of any opioid agonist including tramadol or suboxone
• Change in vasculitis activity in the past 12 weeks, as defined by a change in Physician Global Assessment greater than 1
• Baseline normalized score more than 40 on PROMIS Global Physical Health
• New major medical problem or surgery in past 12 weeks
• Pregnancy or breastfeeding
• Inability to provide informed consent or comply with study procedures
• Schizophrenia or bipolar disorder
• Poorly controlled depression or anxiety, as defined by a score of ≥ 20 on PHQ-9
• Liver cirrhosis
• Significant kidney disease, defined as glomerular filtration rate \<30ml/min

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (7)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15260, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Location

MeSH Terms

Conditions

Churg-Strauss Syndrome; Giant Cell Arteritis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu Arteritis

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Granuloma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Arteritis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Cerebral Small Vessel Diseases; Aortic Arch Syndromes; Aortic Diseases

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Peter A Merkel, MD, MPH

  University of Pennsylvania

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2018
• First Posted: March 29, 2018
• Study Start: February 4, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (6)