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

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  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

This is a multi-center, randomized, double-blind, cross-over, placebo-controlled trial to evaluate the efficacy of low-dose naltrexone (LDN) 4.5 mg nightly in improving self-reported physical health in patients with vasculitis. At study enrollment, each patient will be randomized to receive either LDN for 6 weeks followed by oral placebo for 6 weeks, or placebo for 6 weeks followed by LDN for 6 weeks. The primary outcome measure and some secondary outcome measures are patient-reported and will be recorded every 3 weeks, or every 6 weeks

Arms

Experimental: Naltrexone Hydrochloride

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

Placebo Comparator: Placebo Comparator

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

Interventions

Drug: - Naltrexone Hydrochloride

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

Other: - Placebo Comparator

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