The Safety and Efficacy of an NAD+ Boosting Product Together With a Low Carbohydrate Diet in Adults With Mild Hypertension and Eligible for Normal-standard-of-care

Hypertension Clinical Trial

Official title: An Open Label Study to Investigate the Safety and Efficacy of an NAD+ Boosting Investigational Product Together With a Low Carbohydrate Diet in an Adult Population With Mild Hypertension and Eligible for Normal-standard-of-care

Status Completed

Clinical Trial Summary

The objective of this study is to evaluate the safety and efficacy of Limitless, in combination with a low-carbohydrate diet, after 30 days of supplementation in an adult population. Changes from baseline to Day 30 post-supplementation on several parameters of vascular function will be examined and safety outcomes will be determined.

Clinical Trial Description

With an aging population, and the resulting economic and health burdens, strategies to support healthy aging and mitigate age-associated metabolic changes are essential.

Recent studies have demonstrated that decreases in nicotinamide adenine dinucleotide (NAD+) levels in multiple tissues is involved in the pathogenesis of age-associated diseases. Therefore, strategies to support NAD+ levels and prevent the decline of NAD+ with age have drawn significant attention. NAD+ precursors have also been proposed to augment NAD+ and support healthy aging. While NAD+ precursors share some similarities, there are differences in their bioavailability and safety profiles. Both nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are orally bioavailable and appear to increase NAD+ levels more efficiently than nicotinic acid (NA). Further, a study in rodents suggests that NMN is retained in the body longer than NA. Unlike NMN, NA is associated with several adverse effects such as cutaneous flushing and nausea and hepatoxicity in sustained release-formulations. Recently, the first clinical study examining the safety and bioavailability of NMN supplementation found that single orally administered doses of 100-500 mg were safe and well-tolerated.

The investigational product in this study contains NMN, in addition to berberine, R-lipoic acid, garlic powder, agmatine, black pepper extract, fisetin and L-citrulline malate. Preclinical studies have shown that restoring NAD+ levels by supplementation of NMN can ameliorate some of the functional defects caused by its decline. Further, there are numerous proof-of-concept in vitro and in vivo animal studies indicating that NMN supplementation has beneficial biological effects. Administration of 100 mg/kg/day of NMN for 12-months mitigated age-associated physiological declines in energy metabolism, insulin sensitivity, and plasma lipid profile while age-associated body weight gain was decreased. Other animal studies have shown that NMN supplementation improved glucose intolerance and lipid profiles in models of high-fat-induced and age-induced diabetic mice. Further, 300 mg/kg/day of NMN supplementation for 8 weeks in old mice ameliorated age-associated nitric oxide (NO)-mediated endothelium-dependent dilation and oxidative stress. Despite the promising evidence in pre-clinical models, there have been no reports on the efficacy of NMN supplementation in humans. There are currently five registered clinical trials examining the role of NMN supplementation on metabolic parameters including glucose and insulin metabolism, lipid levels, body composition and hormone levels.

The intervention for this open label study will be Limitless, a supplement containing NAD+ boosting ingredients, in combination with a low carbohydrate diet. This study is a pilot study to provide information on the safety and efficacy of the intervention composed of Limitless and a low-carbohydrate diet on a population of participants that are not eligible for statin therapy. This study will inform on future research to be conducted in randomized, double-blind, placebo-controlled trials designed for chronic supplementation of the investigational product together with the diet. Vascular function will be assessed by blood pressure (BP), blood flow velocity and NO metabolites as well as examine outcomes related to NAD+ metabolism, inflammation and anti-oxidant status, glucose metabolism, lipid profile, physical performance, quality of life and safety. Dietary strategies to modify hypertension have been used as part of standard of care, including the Dietary Approaches to Stop Hypertension (DASH) diet. Other dietary interventions have been used to reduce BP and improve other cardiometabolic markers in otherwise healthy adults. Indeed, both low-carbohydrate and low-fat dietary interventions have been found to reduce systolic BP (SBP) and diastolic BP (DBP) . It is acknowledged that both dietary strategies may be beneficial to this population, however we have selected a low carbohydrate diet as this is hypothesized to be more compatible with the investigational product, Limitless, as a high-carbohydrate diet negates the potential benefits of the supplement. For example, the blood-sugar mediating effects of Berberine, are countered by the blood-sugar spike caused by a carbohydrate rich diet. The carbohydrate rich diet is thought to be one contributor to high blood pressure, therefore a low carbohydrate diet in combination with the supplement is hypothesized to produce beneficial improvements in blood pressure while promoting factors that support restoration of healthy blood flow and oxygen delivery in the body.

Normal-standard-of-care is the recommendation in place for medical practitioners in the management of hypertension prior to the introduction of prescription medication plans. According to the most recent report from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines, lifestyle modifications are recommended prior to prescribing anti-hypertensives. In Hypertension Canada's 2020 Comprehensive Guidelines for Prevention, Diagnoses, Risk Assessment, and Treatment of Hypertension in Adults and Children, patients who are low risk, defined as having no other target organ or cardiovascular risk factors suggest an initiation of anti-hypertensive therapy when systolic SBP is ≥ 160 mmHg, or diastolic DBP is ≥ 100 mmHg.

Participants in this study represent a target population who would benefit from safe and efficacious nutraceuticals for regulation of BP without the added burden of side effects that are associated with angiotensin converting enzyme (ACE) inhibitors thus limiting the complexities of polypharmacy. The current study population therefore allows for hypertensives to be enrolled if they are found to be ineligible for therapeutic plans that required prescription medication of ACE inhibitors. Participants will be assessed on a case-by-case basis to ensure that commodities and concomitant medications that may impact the safe of a passage of a participant thought this study will be monitored. Significant metabolic or physiological conditions that may affect vascular function, inflammation or glucose metabolism will be excluded. As well, an extensive list of exclusions in place will ensure that eligibility is based on establishing health and each participants' eligibility will be overseen by the Medical Director. Participants aged 45 to 65 years will be considered for enrolment to avoid complications related to advanced age and a body mass index (BMI) of and up to 32.9 kg/m2 will eliminate confounders related to advanced obesity. Sex-specific waist circumference cut-offs of less than 102 cm in men and 88 cm in women will be used to exclude individuals with an increased risk for obesity-related diseases. ;

Related Conditions & MeSH terms

• Hypertension

• NCT number: NCT05298410
• Study type: Interventional
• Source: Limitless Research Inc.
• Status: Completed
• Phase: Phase 2
• Start date: March 17, 2022
• Completion date: October 27, 2022