Zinc + Nicotinamide Riboside for Pulmonary Fibrosis

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cedars-Sinai Medical Center

Must be taking: IPF standard care

Must not be taking: Cytotoxic, Immunosuppressive, Prednisone, others

Disqualifiers: Asthma, Tuberculosis, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether combining zinc and nicotinamide riboside (a form of Vitamin B3) can help treat idiopathic pulmonary fibrosis (IPF), a lung disease that causes scarring and breathing problems. Researchers aim to determine if these supplements improve symptoms and quality of life for people with IPF, while also assessing the feasibility of participants joining and completing the trial from home. Participants will be randomly assigned to take either the supplements or a placebo (a substance with no active ingredients) for 24 weeks. This trial suits individuals with a confirmed diagnosis of IPF, who are receiving treatment from a pulmonologist, and reside in certain U.S. states like California or Arizona. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using certain IPF therapies or medications that interact with zinc. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotinamide riboside (NR) is safe for humans. Studies have not found significant side effects when comparing NR to a placebo, a non-active substance. Participants did not experience more negative effects than those taking the placebo. Research also indicates that NR does not negatively affect cholesterol levels or certain body functions.

Zinc, another component of the combination, is a well-known dietary supplement. Most people tolerate it well at normal doses. However, very high doses of zinc can cause side effects like nausea or stomach upset, so following the dosage instructions in any study or treatment plan is important.

Overall, the available data suggest that both zinc and nicotinamide riboside are safe for humans, especially at the doses used in this study. This trial is in the second phase, which usually means researchers have some evidence of the treatment's safety from earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about zinc and nicotinamide riboside as potential treatments for pulmonary fibrosis because these compounds offer a novel approach. Current treatments, like antifibrotic medications, mainly aim to slow disease progression. However, nicotinamide riboside may work by enhancing cellular energy metabolism, which could help repair lung tissue. Zinc, on the other hand, is known for its anti-inflammatory properties, which might reduce the inflammation associated with pulmonary fibrosis. Together, these supplements could offer a complementary strategy to manage and potentially improve lung function in ways existing treatments cannot.

What evidence suggests that zinc and nicotinamide riboside might be an effective treatment for pulmonary fibrosis?

This trial will compare the combination of zinc and nicotinamide riboside to placebos to evaluate their effectiveness in treating idiopathic pulmonary fibrosis (IPF). Studies have suggested that zinc may help repair lung damage and could improve survival rates for people with IPF. Nicotinamide riboside increases NAD+ levels, which are important for cell repair and energy. Early research indicates these supplements might improve symptoms and lung function in people with IPF. ^{1 2 3 4 6}

Who Is on the Research Team?

Tanzira Zaman, MD

Principal Investigator

Cedars-Sinai

Are You a Good Fit for This Trial?

This trial is for individuals with idiopathic pulmonary fibrosis who can perform study procedures from home. They must be able to take supplements twice daily, do lung function tests every 12 weeks, have a CT scan at the start and end of the study, attend video visits every 4 weeks, and complete symptom surveys.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

I can do lung function and 6-minute walk tests every 3 months.

Confident diagnosis of IPF per the latest ATS/ERS/JRS/ALAT Clinical Practice Guideline on Diagnosis of IPF

Exclusion Criteria

I started taking pirfenidone or nintedanib less than 60 days ago.

I haven't taken any strong immune or cancer drugs in the last 60 days.

Any condition that in the opinion of the investigators would confound the ability to interpret data from the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take zinc and nicotinamide riboside supplements twice a day for 24 weeks

24 weeks

Video study visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Outcome Assessment

Participants complete pulmonary function testing and six minute walk tests every 12 weeks, and high resolution CT scans at the start and end of the study

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide riboside
• Placebos for zinc and nicotinamide riboside
• Zinc

Trial Overview The trial is testing if zinc and nicotinamide riboside can improve symptoms or lung function in IPF patients. Participants will receive either these supplements or placebos without active ingredients to compare effects over a period of 24 weeks.

How Is the Trial Designed?

Group I: Combination Supplements Experimental Treatment 2 Interventions

Zinc and nicotinamide riboside

Group II: Placebo Placebo Group 1 Intervention

Placebo-controls for both zinc and nicotinamide riboside

Nicotinamide riboside is already approved in United States, European Union for the following indications:

Approved in United States as Niagen for:

• Dietary supplement for general health and wellness

Approved in European Union as Tru Niagen for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze, D., Brenner, C., Kruger, CL.[2023]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

Nicotinamide riboside (NR) has been shown to prevent and even reverse liver fibrosis in mice, indicating its potential as a protective treatment against liver damage.

The protective effects of NR are linked to its ability to activate Sirt1, which regulates the acetylation of Smads, thereby inhibiting the activation of hepatic stellate cells involved in liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway. Jiang, R., Zhou, Y., Wang, S., et al.[2022]

Long-term supplementation of nicotinamide riboside (NR) over 2 years in individuals with ataxia telangiectasia (A-T) was found to be safe and well tolerated, with most participants experiencing no adverse effects.

The study showed significant improvements in neuromotor function, particularly in coordination and eye movements, with a slower progression of symptoms compared to historical data, indicating potential therapeutic benefits of NR in managing A-T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. Presterud, R., Deng, WH., Wennerström, AB., et al.[2023]

Nicotinamide riboside (NR) supplementation significantly reduced liver fibrosis in a diet-induced mouse model, indicating its potential as a preventative treatment for liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD).

NR was found to inhibit the activation of hepatic stellate cells, which play a key role in liver fibrosis, and also increased energy expenditure, suggesting a mechanism of action that may involve enhancing metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis. Pham, TX., Bae, M., Kim, MB., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06567717

Zinc and Nicotinamide Riboside for Idiopathic Pulmonary ... This trial aims to determine the feasibility of conducting a decentralized randomized controlled trial of zinc and nicotinamide riboside versus matched placebos ...

2. withpower.com withpower.com/trial/zinc-nicotinamide-riboside-for-pulmonary-fibrosis-a1696

Zinc + Nicotinamide Riboside for Pulmonary Fibrosis This trial studies if zinc and nicotinamide riboside can treat IPF, potentially reducing lung scarring by boosting NAD+ levels, compared to placebos.

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/530216

Zinc and Nicotinamide Riboside for Idiopathic Pulmonary ... This trial studies if zinc and nicotinamide riboside can treat IPF, comparing them to placebos to see if they improve symptoms and lung function. Participants ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7277745/

Possible Adverse Effects of High-Dose Nicotinamide Nicotinamide (NAM) at doses far above those recommended for vitamins is suggested to be effective against a wide spectrum of diseases and conditions.

5. cedars-sinai.org cedars-sinai.org/newsroom/zinc-found-to-play-an-important-role-in-lung-fibrosis/

Zinc Found to Play an Important Role in Lung Fibrosis A new study shows that zinc, a common mineral, may reverse lung damage and improve survival for patients with idiopathic pulmonary fibrosis (IPF) ...

6. delta.larvol.com delta.larvol.com/Products/?ProductId=5e2c5a1c-b104-461f-9957-312735ec4a74

Niagen (nicotinamide riboside) / ChromaDex QPRT DEFICIENCY TRIGGERS MITOCHONDRIAL DYSFUNCTION AND POTENTIATES STING-DEPENDENT INFLAMMATION IN INTESTINAL FIBROBLASTS (UEGW 2025) - "While cultivation ...