Metabolic Syndrome, Premature Aging
Conditions
Keywords
NAD+, ATP, Glutathione, Cortisol, Exercise
Brief 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.
Detailed 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.
Interventions
DIETARY_SUPPLEMENTRiaGev
Dietary supplementation
Sponsors
KGK Science Inc.
University of Washington
Bioenergy Life Science, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
randomized, double-blind, comparator-controlled, cross-over
Eligibility
Sex/Gender
ALL
Age
36 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 1 to Day 8 | 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. |
| Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 1 to Day 8 | 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. |
| Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 1 to 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | 7 days | 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. |
| The Waking Salivary Cortisol Level After RiaGev Supplementation | 7 days | 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. |
| The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | 7 days | 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. |
| Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | 7 days | 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. |
| Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | 7 days | 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. |
| Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | 7 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | 7 days | 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. |
| The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | 7 days | 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. |
| The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | 7 days | 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. |
Countries
United States
Participant flow
Recruitment details
Total of 42 subject screened, 18 enrolled into study and randomized into two groups with 9 subjects each.
Participants by arm
| Arm | Count |
|---|---|
| RiaGev, Then Comarator RiaGev, 2000mg, BID, in Period 1, then cross-over to Comparator in Period 2, after 7-day washout. | 9 |
| Comparator, Then RiaGev Comparator, BID, in Period 1, then cross-over to RiaGev 2000mg, BID, in Period 2 after 7-day washout. | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (7 Days) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Comparator, Then RiaGev | RiaGev, Then Comarator | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Continuous | 53.33 Years STANDARD_DEVIATION 7.31 | 50.11 Years STANDARD_DEVIATION 8.62 | 51.72 Years STANDARD_DEVIATION 7.97 |
| BMI | 26.12 Kg/cm^2 STANDARD_DEVIATION 2.75 | 24.29 Kg/cm^2 STANDARD_DEVIATION 2.96 | 25.21 Kg/cm^2 STANDARD_DEVIATION 2.86 |
| Diastolic Blood Pressure | 78.31 mmHg STANDARD_DEVIATION 5.01 | 78.33 mmHg STANDARD_DEVIATION 7.63 | 78.32 mmHg STANDARD_DEVIATION 6.32 |
| Heart Rate | 66.33 bpm STANDARD_DEVIATION 9.11 | 64.11 bpm STANDARD_DEVIATION 19.62 | 65.22 bpm STANDARD_DEVIATION 14.35 |
| Height | 172.67 CM STANDARD_DEVIATION 14.18 | 175.22 CM STANDARD_DEVIATION 8.12 | 173.95 CM STANDARD_DEVIATION 11.09 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 18 Participants |
| Region of Enrollment United States | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
| Systolic Blood Pressure | 124.26 mmHg STANDARD_DEVIATION 9.32 | 124.57 mmHg STANDARD_DEVIATION 13.01 | 124.42 mmHg STANDARD_DEVIATION 11.16 |
| Weight | 79.06 Kg STANDARD_DEVIATION 19.99 | 75.15 Kg STANDARD_DEVIATION 14.6 | 77.11 Kg STANDARD_DEVIATION 17.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 |
| other Total, other adverse events | 1 / 18 | 1 / 17 |
| serious Total, serious adverse events | 0 / 18 | 0 / 17 |
Outcome results
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.
Time frame: Day 1 to Day 8
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 3 over Day 1 | 1.23 MicroMolar | Standard Deviation 3.39 |
| RiaGev | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 5 over Day 1 | 2.12 MicroMolar | Standard Deviation 4.72 |
| RiaGev | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 8 over Day 1 | 1.30 MicroMolar | Standard Deviation 3.2 |
| Comparator | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 3 over Day 1 | 0.13 MicroMolar | Standard Deviation 4.83 |
| Comparator | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 5 over Day 1 | -0.20 MicroMolar | Standard Deviation 2.79 |
| Comparator | Whole Blood NAD+ Level Change Over Baseline After Supplementation | Day 8 over Day 1 | -0.60 MicroMolar | Standard Deviation 2.53 |
Comparison: A comparison between before and after RiaGev supplementation.p-value: 0.034Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation of Comparator.p-value: 0.265Wilcoxon (Mann-Whitney)
Comparison: A comparison between RiaGev and Comparator groups.p-value: 0.044ANCOVA
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.
Time frame: Day 1 to Day 8
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 3 over Day 1 | 1.30 microMolar | Standard Deviation 1.72 |
| RiaGev | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 5 over Day 1 | 1.88 microMolar | Standard Deviation 2.55 |
| RiaGev | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 8 over Day 1 | 1.33 microMolar | Standard Deviation 1.88 |
| Comparator | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 3 over Day 1 | 0.85 microMolar | Standard Deviation 2.49 |
| Comparator | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 5 over Day 1 | 0.51 microMolar | Standard Deviation 1.52 |
| Comparator | Whole Blood NADP+ Level Change Over Baseline After Supplementation | Day 8 over Day 1 | 0.34 microMolar | Standard Deviation 1.34 |
Comparison: A comparison between before and after supplementation of RiaGev.p-value: 0.008Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation with Comparator.p-value: 0.297Wilcoxon (Mann-Whitney)
Comparison: A comparison between RiaGev and Comparator supplementation.p-value: 0.04ANCOVA
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.
Time frame: Day 1 to 8
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 3 over Day 1 | 2.54 microMolar | Standard Deviation 4.6 |
| RiaGev | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 5 over Day 1 | 4.01 microMolar | Standard Deviation 6.57 |
| RiaGev | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 8 over Day 1 | 2.63 microMolar | Standard Deviation 4.3 |
| Comparator | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 3 over Day 1 | 0.97 microMolar | Standard Deviation 7.1 |
| Comparator | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 5 over Day 1 | 0.40 microMolar | Standard Deviation 3.88 |
| Comparator | Whole Blood NAD+ Plus NADP+ Level Change Over Baseline | Day 8 over Day 1 | -0.24 microMolar | Standard Deviation 3.39 |
Comparison: A comparison between before and after RiaGev supplementation.p-value: 0.004Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation with Comparator.p-value: 0.64Wilcoxon (Mann-Whitney)
Comparison: A comparison between RiaGev and Comparator supplementation.p-value: 0.014ANCOVA
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.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Day 1 | 17700.42 (mg/dL)*min | Standard Deviation 2525.3 |
| RiaGev | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Day 8 | 662.50 (mg/dL)*min | Standard Deviation 2031.7 |
| RiaGev | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Change from Day 1 to Day 8 | -1037.92 (mg/dL)*min | Standard Deviation 1590.74 |
| Comparator | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Day 1 | 876.25 (mg/dL)*min | Standard Deviation 1601.18 |
| Comparator | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Day 8 | 574.17 (mg/dL)*min | Standard Deviation 1640.77 |
| Comparator | Serum Glucose Change After RiaGev Supplementation Assessed by OGTT | Change from Day 1 to Day 8 | -302.08 (mg/dL)*min | Standard Deviation 1427.42 |
Comparison: A comparison before and after RiaGev supplementation.p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: A comparison before before and after supplementation with Comparator.p-value: 0.382Wilcoxon (Mann-Whitney)
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.
Time frame: 7 days
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 3 over Day 1 | 61.85 microMolar | Standard Deviation 124.73 |
| RiaGev | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 5 over Day 1 | 70.20 microMolar | Standard Deviation 123.89 |
| RiaGev | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 8 over Day 1 | 9.55 microMolar | Standard Deviation 66.82 |
| Comparator | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 8 over Day 1 | -15.08 microMolar | Standard Deviation 76.05 |
| Comparator | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 3 over Day 1 | 32.43 microMolar | Standard Deviation 130.37 |
| Comparator | Serum Glutathione (GSH + GSSG) Change Over Baseline After RiaGev Supplementation | Day 5 over Day 1 | 15.55 microMolar | Standard Deviation 88.62 |
Comparison: A comparison between before and after RiaGev supplementationp-value: 0.003Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation with Comparator.p-value: 0.766Wilcoxon (Mann-Whitney)
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.
Time frame: 7 days
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 5 | 353.28 microMolar | Standard Deviation 82.03 |
| RiaGev | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 1 (baseline) | 327.10 microMolar | Standard Deviation 42.87 |
| RiaGev | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 3 | 351.18 microMolar | Standard Deviation 75.71 |
| RiaGev | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 8 | 330.40 microMolar | Standard Deviation 41.89 |
| Comparator | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 1 (baseline) | 324.94 microMolar | Standard Deviation 58.55 |
| Comparator | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 5 | 329.27 microMolar | Standard Deviation 94.34 |
| Comparator | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 8 | 326.20 microMolar | Standard Deviation 45.46 |
| Comparator | Serum High Energy Phosphate (ATP + ADP) Concentration After RiaGev Supplementation | Day 3 | 345.98 microMolar | Standard Deviation 102.56 |
Comparison: A comparison between RiaGev and Comparator groups after 7-day supplementation.p-value: 0.029ANCOVA
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.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Day 1 | 4807.42 (microUnit/mL)*min | Standard Deviation 2419.04 |
| RiaGev | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Day 8 | 4672.29 (microUnit/mL)*min | Standard Deviation 2427.27 |
| RiaGev | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Change from Day 1 to Day 8 | -135.13 (microUnit/mL)*min | Standard Deviation 2153.66 |
| Comparator | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Day 1 | 4545.67 (microUnit/mL)*min | Standard Deviation 1915.67 |
| Comparator | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Day 8 | 4410.88 (microUnit/mL)*min | Standard Deviation 1929.12 |
| Comparator | Serum Insulin Change After RiaGev Supplementation Assessed by OGTT | Change from Day 1 to Day 8 | -134.79 (microUnit/mL)*min | Standard Deviation 1830.16 |
Comparison: A comparison between before and after RiaGev supplementationp-value: 0.793Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation with Comparator.p-value: 0.758Wilcoxon (Mann-Whitney)
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.
Time frame: 7 days
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 3 over Day 1 | -9.78 Score on a scale | Standard Deviation 13.45 |
| RiaGev | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 5 over Day 1 | -8.33 Score on a scale | Standard Deviation 12.99 |
| RiaGev | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 8 over Day 1 | -5.78 Score on a scale | Standard Deviation 16.27 |
| Comparator | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 3 over Day 1 | -4.28 Score on a scale | Standard Deviation 5.93 |
| Comparator | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 5 over Day 1 | -2.56 Score on a scale | Standard Deviation 5.66 |
| Comparator | The Change in Checklist Individual Strength (CIS) Questionnaire Outcome After a 7-day Supplementation With Either RiaGev™ or Comparator. | Day 8 over Day 1 | -1.67 Score on a scale | Standard Deviation 7.54 |
Comparison: A comparison between before and after RiaGev supplementation.p-value: 0.014Wilcoxon (Mann-Whitney)
Comparison: A comparison between before and after supplementation with Comparator.p-value: 0.049Wilcoxon (Mann-Whitney)
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.
Time frame: 7 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 1 (baseline) | 0.43 mcg/dL | Standard Deviation 0.15 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 8 | 0.38 mcg/dL | Standard Deviation 0.18 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 3 | 0.40 mcg/dL | Standard Deviation 0.19 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 5 | 0.41 mcg/dL | Standard Deviation 0.32 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 3 over Day 1 | -0.03 mcg/dL | Standard Deviation 0.18 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 5 over Day 1 | -0.02 mcg/dL | Standard Deviation 0.34 |
| RiaGev | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 8 over Day 1 | -0.05 mcg/dL | Standard Deviation 0.19 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 3 over Day 1 | -0.04 mcg/dL | Standard Deviation 0.26 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 5 | 0.57 mcg/dL | Standard Deviation 0.29 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 8 | 0.51 mcg/dL | Standard Deviation 0.22 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 5 over Day 1 | 0.07 mcg/dL | Standard Deviation 0.36 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 1 (baseline) | 0.51 mcg/dL | Standard Deviation 0.24 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 8 over Day 1 | 0.00 mcg/dL | Standard Deviation 0.28 |
| Comparator | The Waking Salivary Cortisol Level After RiaGev Supplementation | Day 3 | 0.47 mcg/dL | Standard Deviation 0.19 |
Comparison: A comparison between RiaGev and Comparator groups.p-value: 0.034ANCOVA
Other Pre-specified
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.
Time frame: 7 days
Population: ITT Populaiton
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Creatinine | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Fasting Blood Glucose | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Alanine Transaminase (ALT) | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Hemoglobin A1c | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Estimated Average Glucose | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Creatine Clearance | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Aspartate Transaminase (AST) | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Chloride | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Potassium | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Sodium | 0 Participants |
| RiaGev | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Bilirubin | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Sodium | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Creatinine | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Creatine Clearance | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Aspartate Transaminase (AST) | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Fasting Blood Glucose | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Alanine Transaminase (ALT) | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Chloride | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Bilirubin | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Potassium | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Hemoglobin A1c | 0 Participants |
| Comparator | The Number of Out-of-norm Clinical Chemistry Parameters When Supplemented With RiaGev or Comparator | Estimated Average Glucose | 0 Participants |
Other Pre-specified
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.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Hemotocrit | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Monocyte Count | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Meran Package Volume | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Eosinophil Counts | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Red Blood Cell Distribution Width | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Basophil Count | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Nucleated Red Blood Cells (NRBCA) | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | White Blood Cell Counts | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Red Blood Cell Counts | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Hemoglobin | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Volume | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Immature Granulocytes (IGAB) | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Hemoglobin | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Neutrophil Counts | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Hemoglobin Concentration | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Instrument Absolute Neotrophil Count (IANC) | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Platelet | 0 Participants |
| RiaGev | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Lymphocyte Count | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Immature Granulocytes (IGAB) | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Hemoglobin | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Hemotocrit | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Hemoglobin Concentration | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Red Blood Cell Distribution Width | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Platelet | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Meran Package Volume | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Nucleated Red Blood Cells (NRBCA) | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Neutrophil Counts | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Lymphocyte Count | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Monocyte Count | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Eosinophil Counts | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Absolute Basophil Count | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Red Blood Cell Counts | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Volume | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Mean Corpuscular Hemoglobin | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | Instrument Absolute Neotrophil Count (IANC) | 0 Participants |
| Comparator | The Number of Out-of-norm Hematology Parameters When Supplemented With RiaGev or Comparator. | White Blood Cell Counts | 0 Participants |
Other Pre-specified
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.
Time frame: 7 days
Population: ITT population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RiaGev | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Systolic Pressure | 0 Participants |
| RiaGev | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Diastolic Pressure | 0 Participants |
| RiaGev | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Heart Rate | 0 Participants |
| Comparator | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Systolic Pressure | 0 Participants |
| Comparator | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Diastolic Pressure | 0 Participants |
| Comparator | The Number of Out-of-norm Vital Signs When Supplemented With RiaGev or Comparator | Heart Rate | 0 Participants |