The Safety and Efficacy Study of RiaGev in Healthy Adults

Metabolic Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Comparator-controlled, Cross-over Study to Investigate the Safety and Efficacy of RiaGev™ in Healthy Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04483011
• Other study ID #: 19RNHB(1918)
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 25, 2019
• Est. completion date: November 30, 2020

Study information

• Verified date: November 2020
• Source: Bioenergy Life Science, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This current randomized, double-blind, comparator-controlled, cross over study investigates the efficacy and safety of RiaGev™ via evaluation of NAD+, ATP, glucose, insulin, glutathione, and cortisol levels in healthy adults of ages 36-65.

Description:

Nicotinamide adenine dinucleotide (NAD+) is one of the essential cofactors required for the proper function of living cells, and depletion in NAD has been correlated to aging individuals as NAD is associated with oxidative stress and energy production. Per the Population Reference Bureau (PRB), it is estimated that by the year 2060, the number of Americans over the age of 65 will double to over 98 million. As well, over the years, there has been a continuous rise in obesity within older Americans, reaching 44% for women and 36% for men in the age range of 65-74. One of the most common chronic diseases that are accompanied by aging and obesity diabetes. In 2016 the WHO reported that approximately 1.6 million deaths were attributed to diabetes. Half of these individuals had high blood glucose before the age of 70. Hence it is crucial to actively control blood glucose and oxidative stress during one's midlife stage.

The investigating product RiaGev™ is the first and only commercially available product that contains Bioenergy Ribose® and vitamin B3. It increases NAD+ in the body efficiently to promote healthy mitochondria, active immunity, and cholesterol reduction. As a result, D-ribose is essential for healthy aging.

Bioenergy Ribose® is a 5-carbon carbohydrate (C5H10O5) called D-ribose designated as a Generally Recognized as Safe (GRAS) substance by the US Food and Drug Administration (FDA). It is produced via the pentose phosphate pathway (PPP), which is fundamental for adenosine triphosphate (ATP) production. The PPP is a rate-limiting step that makes use of a short supply enzyme called glucose-6-phosphate dehydrogenase (G-6-PDH). Supplementation of D-ribose can bypass the PPP and directly contribute to ATP production. In addition, to its function for ATP production D-ribose is a critical element of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and acetyl coenzyme A. Provided there is a reduction in ATP production; aging is frequently due to a decline in mitochondria function. Hence, cell function and integrity are compromised, leading to chronic cardiovascular conditions and fatigue (6). With active D-ribose supplementation, improvements have been noted in several pathological conditions such as chronic fatigue syndrome, fibromyalgia, and myocardial dysfunction. Furthermore, D-ribose demonstrated improvements in athletic performances by recovering ATP levels and repairing cellular damage.

Vitamin B3 is an essential water-soluble vitamin known as either niacin, nicotinic acid, or nicotinamide. It is found in foods such as chicken, beef, fish, nuts, legumes, and grains. Also, vitamin B3 can be obtained from conversions of tryptophan in the body. Therefore, foods with tryptophan such as milk, eggs, meat, and fish are another great source of vitamin B3. Once vitamin B3 is consumed, it is converted into two different active forms called NAD+ or nicotinamide adenine dinucleotide phosphate (NADP). NAD+ and NADP are essential for various metabolic redox processes with oxidized or reduced substrates. Cellular functions like genome integrity, gene expression, and cellular communication are carried out by NAD+ required enzymes. These required enzymes are also crucial for the production of ATP via energy transfer from carbohydrates, fats, and proteins. NADP is involved in fewer reactions than NAD+ such as cholesterol and fatty acid synthesis along with antioxidation. Lack of NAD+ has been associated with a variety of aging-related conditions such as metabolic syndrome, cardiovascular health, and cancer.

This current randomized, double-blind, comparator-controlled, cross over study will investigate the efficacy and safety of RiaGev™ via evaluation of NAD+, glucose, insulin, glutathione, and cortisol levels in healthy adults of ages 36-65.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: November 30, 2020
• Est. primary completion date: July 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 36 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Healthy male and females between the ages of 35 and 65 years of age, inclusive

2. BMI between 18.5 to 29.9 kg/m2, inclusive

3. Female participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal (natural or surgically) for at least 1 year prior to screening

Or,

Females of child-bearing potential must have a negative urine pregnancy test at screening and baseline and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

• Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)

• Double-barrier method

• Intrauterine devices

• Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)

• Vasectomy of partner at least 6 months prior to screening

4. Healthy as determined by laboratory results, medical history, physical exam and EKG

5. Agrees to avoid supplementation with tryptophan and vitamin B3 or its derivatives (niacin, nicotinic acid, niacinamide) one week prior to randomization and during the study

6. Ability to complete maximal and submaximal exercise tests

7. Agrees to maintain current diet and activity level throughout the study

8. Agrees to comply to all study procedures

9. Has given voluntary, written, informed consent to participate in the study

10. Self-reported good sleeper at screening. Have a regular sleep cycle with a bedtime between the approximate hours of 9:00pm and 12:00am and regularly receive between 7-9 hours of sleep, and agrees to maintain this sleep schedule throughout the study.

Exclusion Criteria:

1. Women who are pregnant, breast feeding, or planning to become pregnant during the trial

2. Allergy or sensitivity to investigational product's ingredients or standard meal provided

3. Current or ex-smokers within the past year

4. Major surgery within the past 3 months which may impact the study outcomes to be assessed by the QI.

5. Untreated/unresolved/uncontrolled cardiovascular disease. Participants with no significant cardiovascular event in the past 1 year and on stable medication may be included after assessment by the QI on a case by case basis

6. Self reported current or pre-existing thyroid condition. Treatment on a stable dose medication for over 3 months will be reviewed on a case-by-case basis by the QI

7. Current or history of hypertension.

8. Type I or Type II diabetes

9. Cancer, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable

10. Self reported of any autoimmune disease or immune-compromised

11. Self reported by subjects of being HIV or Hepatitis B/C positive

12. History or currently with kidney and liver diseases assessed by QI on a case by case basis, with the exception of history of kidney stones symptom free for 1 year

13. Known medical or psychological condition that, in the qualified investigator's opinion, could interfere with study participation

14. Significant gastrointestinal disease (examples include but are not limited to Celiac disease and inflammatory bowel disease)

15. Self reported of bleeding disorders.

16. Current diagnosis of gout within past three months as per the QI's assessment

17. Clinically significant abnormal laboratory results at screening as assessed by QI

18. Current use of prescribed medications or over the counter supplements that may interfere with the IP assessed by QI (See Section 7.3)

19. Alcohol consumption of >2 standard drinks/day or >14 drinks/week

20. Alcohol or drug abuse within the past 12 months

21. Use of medical marijuana

22. Frequent use of recreational drugs within 6 months of baseline assessed as per QI

23. Planned blood donation during or within 30 days following conclusion of clinical trial

24. Participation in other clinical research trials 30 days prior to baseline

25. Participants that are cognitively impaired and/or who are unable to give informed consent

26. Any other active or unstable medical condition, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant.

Related Conditions & MeSH terms

• Aging, Premature
• Metabolic Syndrome
• Premature Aging

Intervention

Dietary Supplement:
• RiaGev
Dietary supplementation

Locations

Country	Name	City	State
United States	Prism Research, Inc.	Saint Paul	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Bioenergy Life Science, Inc.	KGK Science Inc., University of Washington

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator	The number of out-of-norm incidence (as indicator of safety) will be reported. Clinical chemistry parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine, electrolytes (Na, K, Cl), fasting glucose. When a parameter is within normal limit, it will been reported as 0 out-of-norm.	7 days
Other	The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator.	The number of out-of-norm hematology parameter incidence (as indicator of safety) will be reported. Hematology parameters include white blood cell (WBC) count with differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), red blood cell (RBC) count, hemoglobin, hematocrit, platelet count, RBC indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW). When a parameter is within normal limits, it is reported as 0 out-of-norm.	7 days
Other	The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator	Vital signs include blood pressure (BP) and heart rate (HR). The number of out-of-norm incidence will be reported. When a parameter is within normal limits, it is reported as 0 out-of-norm.	7 days
Primary	Whole Blood NAD+ Level Change Over Baseline After Supplementation	Whole blood NAD+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. A NAD+ Level change over baseline (Day 1) is calculated by subtracting the NAD+ level at Day 1 ( e.g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated comparing within RiaGev or Comparator group, and between RiaGev and Comparator groups.	Day 1 to Day 8
Primary	Whole Blood NADP+ Level Change Over Baseline After Supplementation	Whole blood NADP+ concentration are measured at Day 1, Day 3, Day 5, and Day 8. NADP+ level changes over baseline (Day 1) are calculated by substracting NADP+ level at Day 1. The significance of change (p values) are calculated comparing changes within and between RiaGev and Comparator groups.	Day 1 to Day 8
Primary	Whole Blood NAD+ Plus NADP+ Level Change Over Baseline	The change in whole blood NAD+ plus NADP+ levels from Day 1 baseline to Day 8 when supplemented with RiaGev™ or comparator. The parameter is measured at Day 1, Day 3, Day 5, and Day 8. A change over baseline is calculated by subtracting Day 1 value. The significance of changes (p value) are calculated by comparing within and between RiaGev and Comparator groups.	Day 1 to 8
Secondary	Serum Glucose Change After RiaGev Supplementation Assessed by OGTT	The serum glucose as assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and on Day 8 after 7-day supplementation with either RiaGev™ or comparator. Incremental Area Under the Curve (iAUC) is used as overall blood glucose. Serum glucose change is calculated by subtracting iAUC on Day 1 from iAUC on Day 8. The significance of change (p value) is calculated by comparing values on Day 8 and Day 1.	7 days
Secondary	Serum Insulin Change After RiaGev Supplementation Assessed by OGTT	Serum insulin is assessed by a standard Oral Glucose Tolerance Test (OGTT) on Day 1 and Day 8 after 7-day supplementation with either RiaGev™ or comparator. Serum insulin change is calculated by substracting its level on Day 1 from Day 8. The significance of change (p value) is calculated by comparing Day 1 and Day 8.	7 days
Secondary	Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation	Total serum Glutathione (GSH + GSSG) is measured on Day 1, Day 3, Day 5 and Day 8. after a 7-day supplementation with either RiaGev™ or comparator. A change over baseline is calculated by subtracting glutathione level on Day 1 baseline (e g Day 5 over Day 1 = Day 5 - Day 1). The significance of change (p value) is calculated within the RiaGev or Comparator group.	7 days
Secondary	Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation	Serum high energy phosphate (ATP + ADP) after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, Day 3, Day 5, and Day 8. Comparison are made between the two groups. The significance (p value) is also calculated between the groups.	7 days
Secondary	The Waking Salivary Cortisol Level After RiaGev Supplementation	The salivary cortisol level after a 7-day supplementation with either RiaGev™ or comparator. The measurement take place on Day 1, 3, 5, and 8. The salivary cortisol level as well as change of salivary cortisol level over baseline (Day 1) are reported. Comparisons are make both between the RiaGev and Comparison groups as well as within RiaGev group against its Day 1 baseline. The corresponding significance (p value) will be calculated.	7 days
Secondary	The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator.	Checklist Individual Strength (CIS) Questionnaire was designed by the Dutch research team of Vercoulen et el, to measure fatigues. A standard CIS Questionnaire contains 20 questions, each scoring 1 to 7, total score 20 - 140, with higher score indicating more tiredness. Thus, a negative value in changing score (such as Day 5 - Day 1 baseline) means reduction of tiredness and verse versa.	7 days