Eosinophilic Granulomatosis With Polyangiitis (EGPA)Phase 2LoDoNaVascNCT03482479
Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
A Phase 2 study testing Naltrexone Hydrochloride in people with Eosinophilic Granulomatosis With Polyangiitis (EGPA) and Churg-Strauss Syndrome (CSS), run by University of Pennsylvania at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Eosinophilic Granulomatosis With Polyangiitis (EGPA), Churg-Strauss Syndrome (CSS), Giant Cell Arteritis
- What is being tested?
- Naltrexone Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 4 Feb 2019to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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
- 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
- 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):
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- 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)
- 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
- Biopsy-proven cutaneous PAN
- 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
- 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.
- 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 -
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84112
About this study
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.
Read the 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
- Conditions
- Eosinophilic Granulomatosis With Polyangiitis (EGPA), Churg-Strauss Syndrome (CSS), Giant Cell Arteritis, Granulomatosis With Polyangiitis, Microscopic Polyangiitis, Polyarteritis Nodosa
- Being tested
- Naltrexone Hydrochloride, Placebo Comparator
- Medical subject headings
- Churg-Strauss Syndrome, Giant Cell Arteritis, Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Polyarteritis Nodosa, Takayasu Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naltrexone HydrochlorideDrug
Naltrexone Hydrochloride will be taken daily (dose 4.5 mg) for six weeks
Placebo ComparatorOther
A placebo tablet which matches the drug will be taken daily for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone Hydrochloride | Experimental | Naltrexone hydrochloride for oral use, 4.5 mg per capsule, taken once a day for 6 weeks. Receives: Other: Placebo Comparator |
| Placebo Comparator | Placebo comparator | Placebo to match naltrexone for oral use to be taken once a day for 6 weeks. Receives: Drug: Naltrexone Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
PROMIS Global Physical Health
Questionnaire about improved health related quality of life to a greater extent than placebo.
Measured: Week 12.
Secondary outcomes (5)
PROMIS Global Physical Health
Questionnaire about improved health related quality of life to a greater extent than placebo.
Measured: 9 weeks
SF-36 (physical component subscore)
Health related quality of life measured by a questionnaire.
Measured: 12 weeks
PROMIS Questionnaires
Questions will ask about anxiety, depression, and sleep disturbance on the PROMIS short form, PROMIS Global Mental Health, and on PROMIS-CAT will ask about physical function, fatigue, satisfaction with social roles, and pain interference, as well in the pain intensity item.
Measured: 12 weeks
Clinical Global Impression of Severity (CGI-S)
7-point scale of patients' self-reporting of severity during the study.
Measured: 12 weeks
Clinical Global Impression of Improvement (CGI-I)
7-point scale of patients' self-reporting of severity during the study.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start4 Feb 2019
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Eosinophilic Granulomatosis With Polyangiitis (EGPA)Studies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter A Merkel, MD, MPH, Study director, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03482479
- Sponsor's protocol ID
- VCRC5564
- Acronym
- LoDoNaVasc
- Status last verified
- Jan 2026
- First submitted
- 22 Mar 2018
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
- ClinicalTrials.gov ID
- NCT03482479
- Acronym / sponsor ID
- LoDoNaVasc / VCRC5564
- Conditions
- Eosinophilic Granulomatosis With Polyangiitis (EGPA), Churg-Strauss Syndrome (CSS), Giant Cell Arteritis, Granulomatosis With Polyangiitis, Microscopic Polyangiitis, Polyarteritis Nodosa
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naltrexone Hydrochloride | Experimental | Other: Placebo ComparatorNaltrexone hydrochloride for oral use, 4.5 mg per capsule, taken once a day for 6 weeks. |
| Placebo Comparator | Placebo comparator | Drug: Naltrexone HydrochloridePlacebo to match naltrexone for oral use to be taken once a day for 6 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
- 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
- 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
- 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):
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naltrexone HydrochlorideNaltrexone Hydrochloride will be taken daily (dose 4.5 mg) for six weeks | Drug | Placebo Comparator |
| Placebo ComparatorA placebo tablet which matches the drug will be taken daily for 6 weeks. | Other | Naltrexone Hydrochloride |
Primary outcome
PROMIS Global Physical Health
Time frame: Week 12.
Questionnaire about improved health related quality of life to a greater extent than placebo.
5 secondary outcomes
PROMIS Global Physical Health
Time frame: 9 weeks
SF-36 (physical component subscore)
Time frame: 12 weeks
PROMIS Questionnaires
Time frame: 12 weeks
Clinical Global Impression of Severity (CGI-S)
Time frame: 12 weeks
Clinical Global Impression of Improvement (CGI-I)
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter A Merkel, MD, MPH study director
University of Pennsylvania
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone Hydrochloride in people with Eosinophilic Granulomatosis With Polyangiitis (EGPA) and Churg-Strauss Syndrome (CSS), run by University of Pennsylvania at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PROMIS Global Physical Health (time frame: Week 12.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.