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          Grants & Funding: The NIAMS Extramural Program
          Clinical Trials in the Spotlight
          Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis








Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis FacebookEmailPrintFacebookEmail     
    Clinical Trials in the Spotlight Main Page

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports a range of clinical trials studying new and existing interventions for prevention and treatment of arthritis, musculoskeletal, and skin diseases.  Investigators supported by the NIAMS need your help finding individuals to participate in clinical trials.  Participating in clinical trials allows you to play an active role as a volunteer in research and contribute to generating new knowledge about the disease/condition, and potentially future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Study Description

Symptoms clearly attributable to inflammatory disease are controllable in the great majority of patients with vasculitis. However, most patients do not feel healthy despite effective immune-suppressive treatment. Among the residual symptoms that disrupt the lives of patients with vasculitis, fatigue, poor physical function, sleep disturbance, and satisfaction with social roles are the most common and have the greatest negative impact on quality of life. Although there are multiple potential sources of these symptoms – residual autoimmune/inflammatory disease, medication side effects, co-morbidities such as obstructive sleep apnea or depression – the cause(s) often defy identification and successful management in the individual patient. Chronic pain is also high on the list of important negative influences on quality of life of patients with vasculitis.

Naltrexone is an opioid antagonist that is used in high doses for emergency treatment of opioid overdose and is FDA approved in an oral daily dose of 50 mg to prevent recidivism in alcoholics. At much lower doses of 4 – 4.5 mg daily, however, it has been shown in small, blinded, randomized trials to improve pain in fibromyalgia, gastrointestinal symptoms in Crohn’s disease, and quality of life in patients with multiple sclerosis.  The mechanism is unclear, with proposals including not only modulation of central pain-processing pathways but also mitigation of inflammatory roles of microglia. In addition to blocking opioid receptors, naltrexone blocks TLR-4, and some studies suggest that the anti-inflammatory effects of low dose naltrexone are independent of opioid receptors.

This multi-center, randomized, double-blinded, cross-over, placebo-controlled trial aims to evaluate the efficacy of low-dose naltrexone (LDN) at 4.5 mg nightly in improving self-reported physical health in patients with vasculitis. The specific aims include 1) determining improvement in physical health during treatment with LDN, using different assessments; 2) determining the change in the severity from baseline during treatment with LDN vs. Placebo in 7 individual domains: physical function, anxiety, depression, fatigue, sleep disturbance, satisfaction with social roles, and pain interferences, as well as with the pain intensity item; 3) determining change in self-reported mental health during treatment with LDN or placebo; 4) determining vasculitis disease activity during treatment with LDN or placebo; and 5) determining the safety of LDN in patients with vasculitis.

**ELIGIBILITY CRITERIA:**

Ages Eligible for Study:           18 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

**Inclusion Criteria:**

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)

	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
		Takayasu’s arteritis: According to an adaptation 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
		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.
		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
			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
			Isolated cutaneous polyarteritis nodosa
			Biopsy-proven cutaneous PAN VCRC5564 LoDoNaVasc
		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
		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
		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 biopsyIf patients have 4 of the above 6 criteria but lack clearcut 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 (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**Study Design:**

Allocation: Randomized

Intervention Model:Crossover Assignment

Masking:Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:Treatment

**Study Location(s):**

Mayo Clinic, Rochester, Minnesota, United States, 55905

University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 15260

University of Utah, Salt Lake City, Utah, United States, 84112

**Study Website:**

https://clinicaltrials.gov/ct2/show/NCT03482479?term=NCT03482479&rank=1


Last Updated: August 2019


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