Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 18-004185
    NCT ID: NCT03482479
    Sponsor Protocol Number: VCRC5564

About this study

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.

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

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)
        • New onset or new type of localized pain in the head
        • Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)
        • ESR of >40 mm in the first hour by Westergren method
        • Temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells
        • 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):
        • Age at disease onset ≤50 years
        • Claudication of extremities
        • Decreased brachial artery pulse (one or both arteries)
        • Blood pressure difference of >10mm Hg between the arms
        • 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):
        • 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
        • Livedo reticularis, cutaneous ulcerations, or skin nodules
        • Testicular pain or tenderness
        • Myalgias
        • Diastolic blood pressure >90mm Hg
        • Elevated BUN or serum creatinine levels
        • 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:
        • Nasal or oral inflammation: painful or painless oral ulcers or purulent or blood nasal discharge
        • Abnormal chest radiograph: nodules, fixed infiltrates, or cavities
        • Urinary sediment: microhematuria or red cell casts
        • Granulomatous inflammation on biopsy: granulomatous inflammation within the wall of an artery or in the perivascular area
        • 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:
        • Necrotizing vasculitis with few or no immune deposits affects small vessel (i.e., capillaries, venules, or arterioles)
        • Necrotizing arteritis involving small and medium-sized arteritis may be present
        • Necrotizing glomerulonephritis is very common
        • 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:
            • Asthma
            • Peak peripheral blood eosinophilia of >10% of total WBC
            • Peripheral neuropathy attributable to vasculitis
            • Transient pulmonary infiltrates on chest imaging studies
            • Paranasal sinus abnormalities or nasal polyposis
            • 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.
  • 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.
  • Age of 18 years or older.
  • Willingness and ability to comply with treatment and follow-up procedures, including receipt of weekly phone calls from the study coordinator.
  • Willingness and ability to provide informed consent. 

Exclusion Criteria:

  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ulrich Specks, M.D.

Open for enrollment

Contact information:

Shannon Daley C.C.R.C., CCRP

(507)293-0637

Daley.Shannon@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

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CLS-20438025

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