Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

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Brief Title

Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

Official Title

Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis

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.
    

Detailed Description

      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
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

PROMIS Global Physical Health

Secondary Outcome

 PROMIS Global Physical Health

Condition

Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Intervention

Naltrexone Hydrochloride

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

36

Start Date

February 4, 2019

Completion Date

December 2021

Primary Completion Date

December 2021

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Peter A Merkel, MD, MPH, 7813214567, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03482479

Organization ID

VCRC5564


Responsible Party

Sponsor

Study Sponsor

University of Pennsylvania


Study Sponsor

Peter A Merkel, MD, MPH, Study Director, University of Pennsylvania


Verification Date

March 2021