Zinc plus nicotinamide riboside for idiopathic pulmonary fibrosis

Feasibility of a Decentralized Double-Blind Randomized Controlled Trial of Zinc and Nicotinamide Riboside for the Treatment of Idiopathic Pulmonary Fibrosis

This study will test whether taking zinc and nicotinamide riboside twice daily helps people over 50 with idiopathic pulmonary fibrosis and whether participants can complete the study remotely while receiving local care.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Cedars-Sinai Medical Center (other)
• Drugs / interventions: prednisone
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT06567717 on ClinicalTrials.gov

What this trial studies

This is a randomized, placebo-controlled Phase 2 trial comparing oral zinc plus nicotinamide riboside to matched placebos over 24 weeks in people with IPF who remain on standard care. The study is designed as a decentralized feasibility trial aiming to recruit 60 participants over 52 weeks and retain them while they take study capsules twice daily. Participants will complete pulmonary function tests and six-minute walk tests with their local pulmonologists every 12 weeks and will undergo high-resolution CT scans at baseline and week 24. The primary objective is to determine whether remote recruitment and local completion of testing are practical, with secondary analyses examining symptoms, quality of life, and lung function changes.

Who should consider this trial

Good fit: Adults over 50 with a confident IPF diagnosis per current ATS/ERS/JRS/ALAT guidelines, under active care by a local pulmonologist, able to take oral medication, and able to use telehealth and local facilities for PFTs, 6MWT, and HRCT are ideal candidates.

Not a fit: People without a confirmed IPF diagnosis, those whose imaging shows more emphysema than fibrosis, those unable to access local testing or telehealth, or individuals under 50 are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, the combination could improve symptoms, quality of life, or lung function for people with IPF and make it easier to join research by allowing remote participation.

How similar studies have performed: Using nicotinamide riboside together with zinc for IPF is largely novel; while NAD+ precursors and zinc have some supportive biological and early-stage data, they have not been proven to treat IPF in prior clinical trials.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Be under active treatment for IPF by a local pulmonologist
4. Age \> 50 years
5. Confident diagnosis of IPF per the latest ATS/ERS/JRS/ALAT Clinical Practice Guideline on Diagnosis of IPF10

   1. Subjects must have a high-resolution computed tomography (HRCT) completed in the 6 months as part of their standard of care prior to informed consent
   2. Subjects must have HRCT pattern of definite or probable UIP
   3. Subjects without HRCT pattern of definite or probable UIP must have surgical lung biopsy as part of their standard of care showing histopathology consistent with UIP
   4. Extent of fibrotic changes must be greater than the extent of emphysema on HRCT
6. Able to take oral medication and willing to adhere to the study treatment regimen
7. Ability to utilize CS-Link, Zoom, or Doximity video conferencing for virtual study visits
8. Ability to complete PFT and 6 minute walk distance test every 12 weeks per standard of care under the order of a local treating pulmonologist
9. Ability to complete HRCT at baseline and 24 weeks per standard of care under the order of a local treating pulmonologist
10. Willingness to participate in home phlebotomy and to travel to a local Quest Diagnostics laboratory
11. Reside in one of the following states: California, Arizona, Georgia, Louisiana, Minnesota, Oregon

Exclusion Criteria:

1. FVC \< 40% of predicted, DLCO \< 30% of predicted, FEV1/FVC with Z-score \< -1.645 or confidence interval \<1.0 within 3 months of screening. If Z-scores or confidence intervals are not available, then FEV1/FVC \< the lower limit of normal will be used as exclusion
2. Evidence of secondary etiologies of ILD (signs/symptoms of connective tissue disease, including ANA titer \> 1:80, history of exposures related to hypersensitivity pneumonitis, history of drug related pulmonary toxicity, occupational exposures)
3. Evidence of comorbid pulmonary pathology including but not limited to asthma, tuberculosis, sarcoidosis, chronic infections
4. Any acute illness or febrile event that has not resolved at least 14 days prior to either screening or the first study visit
5. Use of tobacco-containing products within the last 3 months and/or unwillingness to abstain from use for the duration of the study
6. Participation in a clinical study involving administration of other investigational drugs in the 30 days prior to screening
7. Any condition that in the opinion of the investigators would confound the ability to interpret data from the study
8. Any comorbid condition that is likely to result in death within the next year
9. Inability to obtain reproducible, high-quality pulmonary function tests
10. Likelihood of lung transplantation in the first 12 weeks of the study
11. Use of other IPF-directed therapies beside SOC including but not limited to endothelium receptor antagonists, interferon gamma-1b, N-acetylcysteine
12. Initiation of pirfenidone or nintedanib less than 60 days prior to screening
13. Current therapy or treatment within 60 days prior to screening of any cytotoxic or immunosuppressive medications, cytokine modulating therapies within 4 weeks of the screening visit
14. Chronic prednisone usage at a dose \&amp;gt; 10 mg daily
15. Chronic use of any restricted medications known to have significant interactions with zinc supplementation (see Section 6.5)
16. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
17. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
18. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
19. History of active malignancy in the last 5 years, with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer
20. Prior allogeneic stem cell or solid organ transplantation
21. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications

Where this trial is running

Los Angeles, California

• Cedars-Sinai — Los Angeles, California, United States (RECRUITING)

Study contacts

• Principal investigator: Tanzira Zaman, MD — Cedars-Sinai
• Study coordinator: Study Coordinator

Conditions: Idiopathic Pulmonary Fibrosis, ipf, pulmonary fibrosis, idiopathic pulmonary fibrosis