Using low dose naltrexone to improve health in patients with vasculitis

Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

This study is testing if low dose naltrexone can help improve the quality of life for people with vasculitis.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: prednisone
• Locations: 8 sites (Boston, Massachusetts and 7 other locations)
• Trial ID: NCT03482479 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of low dose naltrexone (LDN) in enhancing health-related quality of life among patients diagnosed with various forms of vasculitis. It is a multi-center, randomized, double-blind, cross-over, placebo-controlled trial where participants will receive either LDN or a placebo for 6 weeks, followed by the alternate treatment for another 6 weeks. The primary and secondary outcomes will be assessed through patient-reported measures collected at regular intervals throughout the study. This approach aims to provide insights into the potential benefits of LDN in managing symptoms associated with vasculitis.

Who should consider this trial

Good fit: Ideal candidates for this study are patients diagnosed with conditions such as eosinophilic granulomatosis with polyangiitis, giant cell arteritis, or other specified forms of vasculitis.

Not a fit: Patients with vasculitis who do not meet the specific diagnostic criteria or those who have contraindications to naltrexone may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could offer a new treatment option to improve the quality of life for patients suffering from vasculitis.

How similar studies have performed: Previous studies have shown promising results for low dose naltrexone in other conditions, suggesting potential efficacy, although this specific application in vasculitis is novel.

Eligibility criteria

Inclusion Criteria:

Patients must meet all of the following criteria in order to be eligible for enrollment:

1. 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

b. Takayasu's arteritis: According to an adaption of the American College of Rheumatology criteria, meeting at least 2 of the following 5 remaining criteria at the time of inclusion of TAK: Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography) (required) i. Age at disease onset ≤50 years ii. Claudication of extremities iii. Decreased brachial artery pulse (one or both arteries) iv. Blood pressure difference of \>10mm Hg between the arms v. Bruit over subclavian arteritis or aorta

c. Polyarteritis nodosa: An adaption of the America College of Rheumatology criteria will be used for the diagnosis of PAN. At the time of inclusion, one major and one minor criteria or two major criteria or isolated cutaneous PAN must be met.

i. Major criteria (not explained by other causes):

1. Arteriographic abnormality
2. Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
3. Mononeuropathy or polyneuropathy ii. Minor criteria (not explained by other causes)

1. 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

1. 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

   f. Eosinophilic granulomatosis with polyangiitis: An adaptation of the American College of Rheumatology criteria will be used for the diagnosis of EGPA. At the time of inclusion, four of the six items must have documented evidence: i. Asthma ii. Peak peripheral blood eosinophilia of \>10% of total WBC iii. Peripheral neuropathy attributable to vasculitis iv. Transient pulmonary infiltrates on chest imaging studies v. Paranasal sinus abnormalities or nasal polyposis vi. Eosinophilic inflammation on tissue biopsy If patients have 4 of the above 6 criteria but lack clear-cut documentation of small vessel vasculitis, they are also eligible for enrollment.
2. Baseline normalized score on PROMIS Global Physical Health of 40 or lower.
3. Vasculitis in remission or very low disease activity, as defined by Physician Global Assessment 0-1 for at least 12 weeks
4. Stable immunosuppressive therapy (including prednisone) related to vasculitis for at least 12 weeks
5. No change in medications in the past 12 weeks made with the expectation of improving pain, fatigue, or mood
6. 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
7. Age of 18 years or older
8. Willingness and ability to comply with treatment and follow-up procedures, including receipt of weekly phone calls from the study coordinator
9. Willingness and ability to provide informed consent -

Exclusion Criteria:

1. 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)
2. Use of another investigational agent as part of a clinical trial within 30 days of enrollment
3. Current use of any opioid agonist including tramadol or suboxone
4. Change in vasculitis activity in the past 12 weeks, as defined by a change in Physician Global Assessment greater than 1
5. Baseline normalized score more than 40 on PROMIS Global Physical Health
6. New major medical problem or surgery in past 12 weeks
7. Pregnancy or breastfeeding
8. Inability to provide informed consent or comply with study procedures
9. Schizophrenia or bipolar disorder
10. Poorly controlled depression or anxiety, as defined by a score of ≥ 20 on PHQ-9
11. Liver cirrhosis
12. Significant kidney disease, defined as glomerular filtration rate \<30ml/min

Where this trial is running

Boston, Massachusetts and 7 other locations

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Completed)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Completed)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States (Completed)
• University of Utah — Salt Lake City, Utah, United States (Completed)
• St. Joseph's Healthcare — Hamilton, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Carol McAlear, MA

Conditions Eosinophilic Granulomatosis With Polyangiitis; Churg-Strauss Syndrome; Giant Cell Arteritis; Granulomatosis With Polyangiitis; Microscopic Polyangiitis; Polyarteritis Nodosa; Takayasu Arteritis