Zinc + Nicotinamide Riboside for Pulmonary Fibrosis

Overseen By Vivian Hwe

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

Trial Summary

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.

What data supports the effectiveness of the treatment Zinc + Nicotinamide Riboside for Pulmonary Fibrosis?

Research shows that nicotinamide and niacin, related to nicotinamide riboside, can reduce lung fibrosis in animal models. Additionally, nicotinamide riboside has shown benefits in reducing liver fibrosis, suggesting potential for similar effects in lung fibrosis. ^{1 2 3 4 5}

Is the combination of Zinc and Nicotinamide Riboside safe for humans?

Nicotinamide riboside (NR), a form of vitamin B3, has been studied for safety and is generally recognized as safe for use in foods and supplements. Studies in animals and humans have shown that NR does not cause significant adverse effects at various doses, although high doses in animals showed some organ toxicity. In human trials, NR was well-tolerated without significant side effects. ^{2 5 6 7 8}

How does the drug Zinc + Nicotinamide Riboside differ from other treatments for pulmonary fibrosis?

Zinc + Nicotinamide Riboside is unique because it combines zinc with nicotinamide riboside, a form of vitamin B3 that boosts NAD+ levels, which may help protect against fibrosis (scarring) in the lungs. This approach is different from other treatments as it focuses on maintaining cellular energy and reducing fibrosis through NAD+ pathways, rather than directly targeting inflammation or fibrosis. ^{2 4 5 6 8}

What is the purpose of this trial?

The goal of this clinical trial is to learn if a clinical trial for idiopathic pulmonary fibrosis (IPF) can recruit and retain participants from their home to study whether a combination of zinc and nicotinamide riboside can treat iIPF. The main questions are: Can the investigators recruit participants, and can participants complete study procedures without physically coming into specific clinical trial sites? Can people with IPF experience improvement in symptoms, quality of life, or functioning if they are take these supplements? The investigators will compare zinc and nicotinamide riboside to matched placebos (look-alike substances that contain no drug) to see if these supplements treat symptoms or lung function in people with IPF. Participants will: Take drug these supplements twice a day for 24 weeks. Complete pulmonary function testing and six minute walk tests with their own pulmonologists every 12 weeks. Complete a high resolution CT scan at the start and end of the study. Complete video study visits with the research team every 4 weeks. Complete surveys about their symptoms and the number of times they take the medication.

Research Team

Tanzira Zaman, MD

Principal Investigator

Cedars-Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Chemoprevention of Lung Carcinogenesis by Dietary Nicotinamide and Inhaled Budesonide. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Effects of nicotinamide and niacin on bleomycin-induced acute injury and subsequent fibrosis in hamster lungs. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway. [2022]

5. Netherlands 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]

7. United States 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. [2021]

8. England 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. [2023]