Characterization of the Effects of Oral NAD+ in a Wellness Cohort
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Pharmacokinetics-NAD+ concentrations
研究概览
简要总结
The goal of this 5 day interventional study was to investigate the effects on multiple biological molecules (multi-omics) of Bryleos's commercially available oral LathMized™ Nicotinamide adenine dinucleotide (LNAD+) supplement in healthy adults aged 45-75 years. The main question to be answered was whether LNAD+ supplementation is associated with change in biological markers relevant to subjects' health. Also, the study determined whether this oral NAD+ formulation raised NAD+ levels including inside blood cells, after the 5 day treatment period, measured on post-treatment Day 1 (Day 6). Thus, the study compared NAD+ levels and impact on biological markers in the LNAD+ arm versus control placebo arm. Safety in this population was assessed using clinical laboratory tests, daily self-reporting of symptoms, and data from a wearable device.
详细描述
The RENEWAL-NAD+ study was designed as a single-center (distributed) Phase 0/1 double-blind, randomized, placebo-controlled clinical trial to evaluate the safety, tolerability, and pharmacodynamic effects of five days of oral LNAD+ (LathMized™ NAD+) in healthy aging adults aged 45 to 75 years (inclusive).
The Renewal-NAD+ study was motivated by the dearth of evidence on oral NAD+ bioavailability and current limited understanding of the mechanisms of action and multi-omic footprint of NAD metabolism interventions from a systems biology standpoint. The present first-in-humans study was designed as a key translational step in establishing the safety, tolerability, and biological effects of LNAD+ in human subjects. The study aimed to demonstrate that theoretical advantages and documented preclinical benefits of enhanced NAD+ delivery translate to meaningful biological changes in healthy aging humans. It also provides meaningful data on the broader biological implications of NAD repletion that could translate into improvements in a multitude of therapeutic areas.
The novel formulation of NAD+ (LNAD+) had been commercially available prior to study initiation and was developed as a systematic formulation approach to the multifaceted barriers that have prevented effective oral NAD+ delivery. The proprietary LathMize™ Technology stabilizes and protects NAD+ before and during GI transit while facilitating absorption through multiple complementary mechanisms including optimizing particle size distribution to enable uptake through multiple pathways.
The study examined the effects of oral LNAD+ supplementation on intracellular and circulating NAD+ levels, as well as on levels of peripheral blood biomarkers, vitals, patient-reported outcomes, activity and sleep measures obtained via a wearable fitness device, and frequency of adverse events in a cohort of healthy adults The study aimed to enroll 60 adults in overall good health to obtain four longitudinal blood draws (two baseline and two on-treatment, respectively) and examined changes in circulating and intracellular NAD+, clinical laboratory tests, and plasma proteome and metabolome composition, in the LNAD+ arm relative to placebo.
The study was designed as a one-center but distributed trial that relied on the combination of ISB BioAnalytica's proprietary Electronic Data Capture (EDC) platform, at-home supplementation by the study participants, and mobile phlebotomy visits for venipuncture and vitals collection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study was double blinded, all investigators, study personnel, molecular facilities and participants were naive to treatment identity.
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •English-speaking adults in the age range between 45 and 75 years in overall self-reported good health (excluding common conditions such as hypertension, and hyperlipidemia);
- •Participants able to consent for themselves;
- •Able to commit to the study protocol, including a 7-day washout of potentially confounding substances via restriction of supplement intake;
- •Tolerance for repeated venous blood draws, supplement administration, and assessment schedule, tolerance for wrist-worn wearable devices well (i.e., consistent use during the day as well as at night for the duration of the study).
排除标准
- •Body Mass Index (BMI) > 35 kg/m2;
- •Current chronic or acute infectious diseases (e.g., hepatitis, influenza, HIV, Lyme; COVID-19 within the past two months);
- •Recent SARS-CoV-2 vaccine administration (within two weeks);
- •Current use of NAD+ supplements and precursors;
- •Use of systemic anti-inflammatory medications (excluding NSAIDs and acetaminophen), immunosuppressants;
- •Current cancer or hematologic conditions and/or cancer treatment (radiation, chemotherapy);
- •Type I juvenile or Type 2 diabetes mellitus;
- •Autoimmune disorders (multiple sclerosis, lupus, rheumatoid arthritis, psoriasis);
- •Inflammatory bowel disease (ulcerative colitis, Crohn's disease);
- •Current pregnancy;
- •Current substance abuse, including alcohol, but excluding nicotine and prescription medications (e.g., physician-prescribed stimulants, opiates);
- •Members of the same household.
研究组 & 干预措施
Treatment arm
LNAD+ (50%)/PEG (50%) treatment total 500 mg
干预措施: LathMized TM NAD+ (LNAD+) (Dietary Supplement)
Control arm
PEG 500 mg
干预措施: Control (placebo) (Other)
结局指标
主要结局
Pharmacokinetics-NAD+ concentrations
时间窗: From enrollment through seven day washout, 2 baseline measurements); treatment 5 days, measured on day 3 and one day post day 5 treatment (Day 6)]
All primary endpoint NAD+ measurements were performed by a CLIA-certified laboratory (Augusta, GA, USA). The proprietary validated enzymatic assay quantifies total NAD (NAD+ plus NADH) in both intracellular (icNAD) and circulating (cirNAD) compartments. The assay specifically quantifies total NAD, reflecting technical considerations and the current state of clinical validation for NAD+/NADH ratio measurements. For most clinical applications, including assessment of supplementation efficacy, total NAD levels can be considered the primary actionable biomarker.
次要结局
- Pharmacodynamic Endpoints: Metabolic Fate(From enrollment through seven day washout, (2 baseline measurements); treatment 5 days, measured on day 3 and one day post day 5 treatment (Day 6))
- Pharmacodynamic Endpoints:Liver Function(From enrollment through seven day washout, (2 baseline measurements); treatment 5 days, measured on day 3 and none day post day 5 treatment (Day6)])
- Pharmacodynamic Endpoints: Oxidative Stress(From enrollment through seven day washout, (2 baseline measurements); treatment 5 days, measured on day 3 and none day post day 5 treatment (Day6)])
- Pharmacodynamic Endpoints: Glucose Metabolism(From enrollment through seven day washout, 2 baseline measurements); treatment 5 days, measured on day 3 and one day post day 5 treatment (Day 6)])
- Pharmacodynamic Endpoints: Lipid Metabolism(From enrollment through seven day washout, (2 baseline measurements); treatment 5 days, measured on day 3 and one day post day 5 treatment (Day 6))
- Pharmacodynamic Endpoints: Inflammation(From enrollment through seven day washout, 2 baseline measurements); treatment 5 days, measured on day 3 and one day post day 5 treatment (Day 6)])
- Pharmacodynamic Endpoint: Kidney Function(From enrollment through seven day washout, (2 baseline measurements); treatment 5 days, measured on day 3 and none day post day 5 treatment (Day6)])
- Physical Safety Measures: Vitals(Time Frame: From enrollment to end of treatment day 5 (measured post treatment Day 1 [Day6]))
- Physical Safety Measures: Adverse Events(From enrollment to end of treatment day 5 (measured post treatment Day 1[Day6])
- Physical Safety Measures: Physical Symptoms(From enrollment to end of treatment day 5 (Measured post treatment day 5 [Day6]))
- Physical Safety Measures: subjective measures of well-ing(From enrollment to end of treatment day 5 (Measured post treatment day 5 [Day6]))
- Physical Safety Outcome Measures: Wearables Data(From first day of study washout period to end of treatment day 5 (Measured post treatment day 5 [Day6]))
- Physical Safety Measures: Vitals(From enrollment to end of treatment day 5 (measured post treatment Day 1(Day 6)])