Antioxidant Supplements for Cystic Fibrosis

Overseen By Paula Rodriguez Miguelez, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Virginia Commonwealth University

Must be taking: CF-antioxidants

Must not be taking: Vasoactive medications

Disqualifiers: Heart disease, PAH, B. Cepacia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether antioxidant supplements can help people with cystic fibrosis (CF) improve their exercise capacity. Participants with CF will receive either resveratrol (a type of antioxidant), NR (another antioxidant), or a placebo to determine which is most effective. Eligible participants must have a CF diagnosis, stable health for the past four weeks, and the ability to perform breathing tests reliably. As an Early Phase 1 trial, participants will be among the first to investigate how these antioxidants affect people with CF, potentially contributing to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications like nitrates, beta-blockers, or Viagra.

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

Research has shown that resveratrol, a natural substance found in some plants, has been studied for its effects on cystic fibrosis (CF). These studies suggest that resveratrol might help improve certain cell functions related to CF. However, most of this research has occurred in labs, not on people, so little is known about its safety in humans.

This trial is in an early stage, likely testing the safety and side effects of resveratrol for the first time. While resveratrol is found in foods and supplements and is generally considered safe, its safety in higher doses or for specific conditions like CF needs verification.

Nicotinamide riboside (NR) is another supplement under testing. Like resveratrol, little safety information exists for people with CF. This early-phase study aims to determine how well people can tolerate these supplements and what side effects might occur.

For those considering joining this trial, early-phase studies are crucial for learning about safety and side effects. Participants play a key role in helping researchers gather this important information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for cystic fibrosis because they explore new ways to tackle the disease using antioxidants. Unlike traditional therapies that often focus on managing symptoms or improving lung function, these treatments use NR (nicotinamide riboside) and resveratrol, both known for their antioxidant properties. NR is believed to boost cellular energy and repair, while resveratrol may reduce inflammation and oxidative stress. These unique mechanisms offer a fresh approach that could complement existing treatments like mucolytics and antibiotics, potentially enhancing overall patient health and quality of life.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

Research suggests that resveratrol, one of the treatments under study in this trial, might help people with cystic fibrosis (CF). Studies have found that resveratrol can improve the movement of important proteins in cells, a common issue in CF. It also boosts the activity of a key protein called CFTR, which aids in saliva flow and airway moisture, potentially easing breathing. However, not all studies agree, and some indicate it might not work well on its own. Overall, resveratrol appears promising, but more research is needed to confirm its benefits for people with CF. ^{1 4 5 6 7}

Who Is on the Research Team?

Paula Rodriguez Miguelez, PhD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Cystic Fibrosis who can perform lung function tests and have an FEV1 percent predicted above 40%. They must not be current smokers, pregnant, or nursing, and should be clinically stable without recent exacerbations or heart disease.

Inclusion Criteria

I have been medically stable for the last 4 weeks.

You may or may not have diabetes related to cystic fibrosis.

I have been diagnosed with cystic fibrosis.

Exclusion Criteria

I have not had a fever or flu-like illness in the last 4 weeks.

I have been diagnosed with heart disease.

Patients with B. Cepacia infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive antioxidant supplements or placebo to assess impact on exercise intolerance

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NR
• Placebo
• Resveratrol

Trial Overview The study is testing the effects of antioxidant supplements Resveratrol and NR on exercise intolerance in CF patients compared to a placebo. Participants will receive one of these treatments to see if it improves their ability to exercise.

How Is the Trial Designed?

Group I: B: Healthy Controls Experimental Treatment 2 Interventions

Healthy controls will be randomly assigned to NR or placebo

Group II: B: Cystic Fibrosis Experimental Treatment 2 Interventions

Patients with CF will be randomly assigned to NR or placebo.

Group III: A: Healthy Controls Experimental Treatment 2 Interventions

Healthy controls will be randomly assigned to resveratrol or placebo

Group IV: A: Cystic fibrosis Experimental Treatment 2 Interventions

Patients with CF will be randomly assigned to resveratrol or placebo.

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Published Research Related to This Trial

Red wines contain significantly higher levels of beneficial compounds like resveratrol and piceid, averaging 4.37 mg/liter, compared to only 0.68 mg/liter in white wines, suggesting a stronger protective effect against cardiovascular disease from red wine consumption.

The study analyzed 42 wines from various regions in Japan, confirming that specific grape varieties, such as Pinot noir, Merlot, and Zweigeltrebe, have particularly high resveratrol content, which may contribute to their health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. Sato, M., Suzuki, Y., Okuda, T., et al.[2019]

Trans-resveratrol (t-RESV), found in grape skins and red wine, shows significant anti-inflammatory and anticarcinogenic properties in various experimental models, highlighting its potential as a therapeutic agent.

The cis isomer of resveratrol (c-RESV) is less studied and not commercially available, leading to a gap in understanding its pharmacological effects compared to the well-researched t-RESV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative studies of the antioxidant effects of cis- and trans-resveratrol. Orallo, F.[2022]

A double-blind, randomized, placebo-controlled trial involving 32 overweight older adults showed that resveratrol supplementation at doses of 300mg and 1000mg per day is safe and well-tolerated, with no significant adverse effects reported.

Participants taking resveratrol experienced significantly lower glucose levels compared to those on placebo, suggesting potential benefits for metabolic health, although their glucose levels did not differ from their baseline measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study. Anton, SD., Embry, C., Marsiske, M., et al.[2022]

Trans-resveratrol is primarily metabolized into two main forms: trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate, which were found abundantly in rat urine and mouse serum, indicating effective metabolism in the body.

The study found virtually no unconjugated resveratrol in urine or serum samples, suggesting that previous in vitro studies using only unconjugated resveratrol may not accurately reflect its metabolism and effects in living organisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human, rat, and mouse metabolism of resveratrol. Yu, C., Shin, YG., Chow, A., et al.[2019]

This study analyzed the content of trans- and cis-resveratrol in 18 commercial Serbian wines, revealing that trans-resveratrol was present in all but one sample, with concentrations ranging from 0.11 to 1.69 mg/L.

Cis-resveratrol was found in 12 out of the 18 wines, with levels between 0.12 and 1.49 mg/L, indicating that Serbian wines contain significant amounts of these beneficial compounds, which are associated with various health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of trans- and cis-resveratrol in Serbian commercial wines. Cvejic, JM., Djekic, SV., Petrovic, AV., et al.[2019]

Citations

1. journals.biologists.com journals.biologists.com/bio/article/4/7/929/1459/Resveratrol-increases-F508del-CFTR-dependent

Resveratrol increases F508del-CFTR dependent salivary ... Our data support the view that resveratrol is beneficial for treating CF. The salivary secretion assay has a potential application to test ...

2. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0081589

Resveratrol Enhances Airway Surface Liquid Depth in ... The present findings strongly indicate that resveratrol activates CFTR and enhances ASL depth. The drug was shown by single channel patch clamp analysis to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7347275/

Resveratrol restores intracellular transport in cystic fibrosis ... The above data demonstrate that resveratrol treatment significantly improves both microtubule structure and intracellular transport in CF-model cells. We have ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304416515002299

Evidence against resveratrol as a viable therapy for the ... Taken together, our results do not support the use of resveratrol supplements as a therapy for patients with cystic fibrosis. It is possible that further ...

5. 2024.sci-hub.se 2024.sci-hub.se/8096/5c3549066831ad32eca09911dd2089e3/lu2020.pdf

Resveratrol restores intracellular transport in cystic fibrosis ... alterations can have important consequences ... Consistent with CF cell data, resveratrol (50 µM, 24 h) treatment completely ... ibuprofen in cystic fibrosis: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4579062/

Resveratrol Ameliorates Abnormalities of Fluid and Electrolyte ... Because resveratrol is a robust CFTR channel potentiator in sinonasal epithelia, we hypothesized that the drug could ameliorate acquired CFTR dysfunction ...

7. mdpi.com mdpi.com/2072-6643/15/2/314

Can Bioactive Food Substances Contribute to Cystic ... Many bioactive food components, such as phytochemicals, polyunsaturated fatty acids, and antioxidants have favorable effects in the management of CF.