Bioavailability of PRUVIN® and Its Effects in Healthy Subjects (INDIGO)

Study Overview
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Brief Summary
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To evaluate the effect of different doses of PRUVIN® (N-acetylcysteine [NAC] and glycine) on reduced glutathione levels in healthy elderly subjects

Detailed Description
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This is a single-center, double-blind, randomized, placebo-controlled 4-arm study-design, to assess the safety, tolerability and effect of PRUVIN® on reduced glutathione levels in healthy elderly (age 60-85 years) subjects. In addition, baseline values of glutathione precursors, glutathione, and plasma markers of oxidative stress in a healthy young cohort (non-interventional) will be compared with those of the healthy elderly cohort (interventional).

Official Title
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Investigation on the Bioavailability of PRUVIN® and Its Effects on Physiologic-metabolic Biomarkers in Healthy Subjects

Conditions
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Oxidative Stress

Intervention / Treatment
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* Dietary Supplement: Pruvin R
* Other: Isomaltulose


Participation Criteria
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Eligibility Criteria
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Non-interventional cohort: Inclusion criteria: 20-40 years, both inclusive male and female Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator. BMI >18.5 and <30.0 kg/m2 HbA1c <5.7 % Informed consent as documented by signature Exclusion criteria: Receipt of any medicinal product or nutritional product in clinical development within 30 days before enrollment in this trial. Any history or presence of clinically relevant comorbidity, as judged by the Investigator. Signs of acute illness as judged by the Investigator. Any serious systemic infectious disease during four weeks prior enrollment in this trial Clinically significant abnormal screening laboratory tests, as judged by the Investigator. AST and/or ALT > 2 times the upper limit of normal. Elevated serum creatinine values above the upper limit of normal. Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or >89 mmHg (excluding white-coat hypertension; therefore, a repeat test showing results within range will be acceptable). Heart rate at rest outside the range of 50-90 beats per minute. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator. Significant history of alcoholism or drug abuse as judged by the Investigator consuming more than 24 grams alcohol/day (for males), 12 grams alcohol/day (for females) on average. Smoking or use of nicotine substitute products. Any medication (prescription and non-prescription drugs) within 14 days before screening. Blood donation or blood loss of more than 500 mL within the last 3 months prior to screening. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation. If female, pregnant or breast-feeding. Consumption of high protein supplements within 60 days of screening and during the study. Consumption of any antioxidant, vitamins, and herbals (see chapter 12.2) supplements within 2 weeks prior to screening and during the study. Interventional Cohort: Inclusion Criteria: 60-85 years, both inclusive male and female Sedentary, less than 1h of strenuous physical exercise per week BMI of 25.0 to 35.0 kg/m2, both inclusive HbA1c<6.5 % Informed consent as documented by signature Exclusion Criteria: Known or suspected hypersensitivity to any component of the trial products. Receipt of any medicinal product or nutritional product in clinical development within 30 days before randomisation in this trial. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction. Any history or presence of clinically relevant comorbidity, as judged by the Investigator. Signs of acute illness as judged by the Investigator. Any serious systemic infectious disease during four weeks prior to first intake of the trial product, as judged by the Investigator. Clinically significant abnormal screening laboratory tests, as judged by the Investigator. AST and/or ALT > 2 times the upper limit of normal. Elevated serum creatinine values above the upper limit of normal. Systolic blood pressure < 90 mmHg or >139 mmHg and/or diastolic blood pressure < 50 mmHg or >89 mmHg (excluding white-coat hypertension; therefore, a repeat test showing results within range will be acceptable). Heart rate at rest outside the range of 50-90 beats per minute. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator. Significant history of alcoholism or drug abuse as judged by the Investigator consuming more than 24 grams alcohol/day (for males), 12 grams alcohol/day (for females) on average. Smoking more than 5 cigarettes or the equivalent per day. Inability or unwillingness to refrain from smoking and use of nicotine substitute products 3 days prior and during the intervention.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, Placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 7.2 g of actives (3.6 g NAC and 3.6 g glycine) per day split in two doses (arm A)<br>First dose (1.8 g NAC and 1.8 g glycine) consumed in the morning Second dose (1.8 g NAC and 1.8 g glycine) taken in the evening | Dietary Supplement: Pruvin R<br>* Combination of N-acetylcysteine an glycine<br>|
| Active Comparator: 4.8 g of actives (2.4 g NAC and 2.4 g glycine) per day split in two doses (arm B)<br>First dose (1.2 g NAC and 1.2 g glycine, +1.2 g placebo) consumed in the morning Second dose (1.2 g NAC and 1.2 g glycine, +1.2 g placebo) taken in the evening | Dietary Supplement: Pruvin R<br>* Combination of N-acetylcysteine an glycine<br>|
| Active Comparator: 2.4 g of actives (1.2 g NAC and 1.2 g glycine) per day split in two doses (arm C)<br>First dose (0.6 g NAC and 0.6 g glycine, +2.4 g placebo) consumed in the morning Second dose (0.6 g NAC and 0.6 g glycine, +2.4 g placebo) taken in the evening | Dietary Supplement: Pruvin R<br>* Combination of N-acetylcysteine an glycine<br>|
| Placebo Comparator: Placebo control (7.2 g isomaltulose)(arm D)<br>First dose (3.6 g isomaltulose) consumed in the morning Second dose (3.6 g isomaltulose) taken in the evening | Other: Isomaltulose<br>* Placebo as comparator to intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total reduced glutathione | Total reduced glutathione (GSH-T) in whole-blood normalized to hematocrit | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free reduced glutathione | Free reduced glutathione (GSH-F), free reduced glutathione to oxidized glutathione disulfide ratio (GSH-F:GSSG) | 2 weeks | 
| Hematocrit | Whole-blood concentrations of glycine and cysteine normalized to hematocrit | 2 weeks | 
| Lipid oxidation | Lipid oxidation derived from indirect calorimetry | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glutathione