Inflammation in COPD and the Effect of Nicotinamide Riboside (ICON)
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ClinicalTrials.gov Identifier: NCT04990869 |
Recruitment Status :
Completed
First Posted : August 5, 2021
Last Update Posted : March 15, 2024
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Tracking Information | |||||
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First Submitted Date ICMJE | June 28, 2021 | ||||
First Posted Date ICMJE | August 5, 2021 | ||||
Last Update Posted Date | March 15, 2024 | ||||
Actual Study Start Date ICMJE | August 5, 2021 | ||||
Actual Primary Completion Date | August 18, 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Interleukin-8 [ Time Frame: 6 weeks ] Measured in sputum
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||
Descriptive Information | |||||
Brief Title ICMJE | Inflammation in COPD and the Effect of Nicotinamide Riboside | ||||
Official Title ICMJE | Effects of Nicotinamide Riboside on the Airway Inflammation of Older Adults With COPD: A Randomized, Double-blind, Placebo-controlled Clinical Trial (NR-COPD) | ||||
Brief Summary | The aim of this study is to investigate if nicotinamide riboside can reduce the airways inflammation associated with chronic obstructive pulmonary disease (COPD) in patients aged 60 or older. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. The investigators hypothesize that six weeks of nicotinamide riboside supplementation reduces interleukin-8 measured in sputum from COPD patients. Further, it is hypothesized that augmentation of NAD+ in COPD patients might alleviate symptoms through activation of sirtuins. | ||||
Detailed Description | Chronic obstructive pulmonary disease (COPD) is a major problem that affect more and more people worldwide with over three million deaths reported every year. COPD has been described as a disease of accelerated lung aging and is associated with oxidative stress and an increased inflammatory response to for instance viral infections. Therefore, in the current pandemic COPD patients are considered at high risk of COVID-19-related death and interventions in this group are crucial. A major event in aging is the loss of nicotinamide adenine dinucleotide (NAD+)-a loss which may be important in promoting the pro-inflammatory environment that occur with aging and therefore possibly COPD. Indeed, NAD+ is emerging as a central metabolic molecule involved in multiple age-related pathways including inflammation and metabolic control. Recently, it was shown that age-associated NAD+ loss is due to macrophage M1-polarization, suggesting that NAD+ is required for macrophage activation, an event that is involved in the pulmonary inflammatory response. In humans, the therapeutic potential of boosting NAD+ levels through supplementation with one of its more bioavailable precursors has therefore gained attention. Nicotinamide riboside (NR) is a NAD+ precursor and recent work suggests that aging can be ameliorated by even short-term treatment with NR. This vitamin B3-analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. Notably, NR treatment in humans decreases circulating markers of inflammation. In addition, NAD+ replenishment may facilitate overall greater resilience of older patients considering the anti-aging effects of NR allowing these patients to better cope with infections. Interestingly, NR has been shown to return aging tissues to a younger state, possibly through augmentation of the sirtuin enzyme family-known to play an important role in almost all cellular functions. COPD patients have reduced sirtuin levels in the airways likely due to oxidative stress. Because sirtuins are NAD+-dependent, supplementation with NR could serve as a treatment option for patients with COPD through activation of sirtuins. In addition, NAD+ replenishment may facilitate overall greater resilience of older patients considering the anti-aging effects of nicotinamide riboside allowing these patients to better cope with infections. The chosen dosage is 2 g per day given orally. This dose has been shown to be safe and tolerated. The dose will be split in two with ingestion of 1 g in the morning and 1 g in the evening. NR is a naturally occurring vitamin B3 analog produced by yeast and found in multiple food products at low concentration. Many organisms including humans cannot produce NR but have instead evolved methods to convert this into the central redox modulator NAD+. The efficacy and safety of NR supplementation has been tested in a number of studies in both healthy middle-aged and older adults and in patients suffering from metabolic disease. Since this is a natural compound widely found in nature no subjects have yet developed allergic responses to the molecule, and repeated doses of up to 2 g orally per day have demonstrated an acceptable safety profile. No treatment-emergent adverse events have so far been reported for NR. Older adults (age ≥ 60 years) with a diagnosis of COPD will be recruited from the Respiratory Medicine and Emergency departments at Bispebjerg Hospital, Denmark, and through advertisements on online websites (e.g. www.lungeforskning.dk). Lung-healthy controls will be recruited through online websites (e.g. www.forsøgsperson.dk). Potential participants will be asked if they want to participate in this trial and informed about the study procedures. If they agree and if they meet the inclusion and not the exclusion criteria, the subjects will be randomized to either the NR or placebo group. All subjects that give informed consent to participate will receive a study identification number. Study endpoints will be assessed at baseline, after the 6-week treatment and follow-up after 18 weeks. Telephone follow-up will be conducted after 58 weeks. Endpoints include airway inflammation measured in sputum, untargeted RNA sequencing of nasal epithelial cells, DNA methylation and untargeted metabolomics in peripheral mononucleated cells, circulating inflammatory markers and NAD+ levels in whole-blood, in addition to clinical outcomes such as lung function (spirometry), chest x-ray and questionnaires. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Not Applicable | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Randomized, double-blind, placebo-controlled Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Primary Purpose: Treatment |
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Condition ICMJE | COPD | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
60 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Actual Study Completion Date ICMJE | August 18, 2022 | ||||
Actual Primary Completion Date | August 18, 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria COPD patients:
Exclusion Criteria COPD patients:
Inclusion Criteria Controls:
Exclusion Criteria Controls:
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Sex/Gender ICMJE |
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Ages ICMJE | 60 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | Yes | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Denmark | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04990869 | ||||
Other Study ID Numbers ICMJE | NR-COPD | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Morten Scheibye-Knudsen, University of Copenhagen | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | University of Copenhagen | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of Copenhagen | ||||
Verification Date | March 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |