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

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

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

Study Overview

• Status: Completed
• Conditions: Oxidative Stress
• Intervention / Treatment: Dietary supplement: Pruvin R; Other: Isomaltulose

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Non-interventional cohort:

Inclusion criteria:

1. 20-40 years, both inclusive
2. male and female
3. Considered generally healthy upon completion of medical history and screening safety assessments, as judged by the Investigator.
4. BMI >18.5 and <30.0 kg/m2
5. HbA1c <5.7 %
6. Informed consent as documented by signature

Exclusion criteria:

1. Receipt of any medicinal product or nutritional product in clinical development within 30 days before enrollment in this trial.
2. Any history or presence of clinically relevant comorbidity, as judged by the Investigator.
3. Signs of acute illness as judged by the Investigator.
4. Any serious systemic infectious disease during four weeks prior enrollment in this trial
5. Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
6. AST and/or ALT > 2 times the upper limit of normal.
7. Elevated serum creatinine values above the upper limit of normal.
8. 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).
9. Heart rate at rest outside the range of 50-90 beats per minute.
10. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator.
11. 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.
12. Smoking or use of nicotine substitute products.
13. Any medication (prescription and non-prescription drugs) within 14 days before screening.
14. Blood donation or blood loss of more than 500 mL within the last 3 months prior to screening.
15. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation.
16. If female, pregnant or breast-feeding.
17. Consumption of high protein supplements within 60 days of screening and during the study.
18. 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:

1. 60-85 years, both inclusive
2. male and female
3. Sedentary, less than 1h of strenuous physical exercise per week
4. BMI of 25.0 to 35.0 kg/m2, both inclusive
5. HbA1c<6.5 %
6. Informed consent as documented by signature

Exclusion Criteria:

1. Known or suspected hypersensitivity to any component of the trial products.
2. Receipt of any medicinal product or nutritional product in clinical development within 30 days before randomisation in this trial.
3. History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
4. Any history or presence of clinically relevant comorbidity, as judged by the Investigator.
5. Signs of acute illness as judged by the Investigator.
6. Any serious systemic infectious disease during four weeks prior to first intake of the trial product, as judged by the Investigator.
7. Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
8. AST and/or ALT > 2 times the upper limit of normal.
9. Elevated serum creatinine values above the upper limit of normal.
10. 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).
11. Heart rate at rest outside the range of 50-90 beats per minute.
12. Clinically significant abnormal standard 12-lead electrocardiogram (ECG) after 5 minutes resting in supine position at screening, as judged by the Investigator.
13. 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.
14. Smoking more than 5 cigarettes or the equivalent per day.
15. Inability or unwillingness to refrain from smoking and use of nicotine substitute products 3 days prior and during the intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

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); 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; Combination of N-acetylcysteine an glycine
Active Comparator: 4.8 g of actives (2.4 g NAC and 2.4 g glycine) per day split in two doses (arm B); 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; Combination of N-acetylcysteine an glycine
Active Comparator: 2.4 g of actives (1.2 g NAC and 1.2 g glycine) per day split in two doses (arm C); 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; Combination of N-acetylcysteine an glycine
Placebo Comparator: Placebo control (7.2 g isomaltulose)(arm D); First dose (3.6 g isomaltulose) consumed in the morning; Second dose (3.6 g isomaltulose) taken in the evening	Other: Isomaltulose; Placebo as comparator to intervention

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nestlé

Publications and helpful links

General Publications

• Lizzo G, Migliavacca E, Lamers D, Frézal A, Corthesy J, Vinyes-Parès G, Bosco N, Karagounis LG, Hövelmann U, Heise T, von Eynatten M, Gut P. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging. 2022 Mar 7;3:852569. doi: 10.3389/fragi.2022.852569. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): May 1, 2020

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Glutathione
• Other Study ID Numbers: 18.01.CLI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No