Clinical trial NCT07024966: Effect of the Combination of Pterostilbene Cocrystal With Silybin and Nicotinamide Riboside on Exercise-Induced Oxidative Stress
Official title: Effect of the Combination of Pterostilbene Cocrystal With Silybin and Nicotinamide Riboside on High-Intensity Exercise-Induced Oxidative Stress: A Randomized, Crossover, Placebo-Controlled, Triple-Blind Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Oxidative Stress
Physical Activity
Antioxidant Effect
Keywords: Oxidative Stress
High-intensity exercise
Pterostilbene
Antioxidant supplement
Nutraceutical
Crossover trial
Exercise recovery
Nutritional intervention
Polyphenols
Cocrystal
Lead sponsor: Fundació Eurecat
Sponsor class: OTHER
Collaborators: name: Circe, S.L.
First posted: 2025-06-17
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This study aims to evaluate the effects of the dietary supplement ccPT-SIL-NR, which contains pterostilbene (ccPT), silybin (SIL), and nicotinamide riboside (NR), on oxidative stress markers after a high-intensity exercise session. The primary objective is to assess changes in blood malondialdehyde (MDA) levels.

Secondary objectives include evaluating the effects on oxidative DNA damage (8-OHdG), lipid peroxidation (F2-isoprostanes), total antioxidant capacity (FRAP assay), glutathione ratio (GSH/GSSG), antioxidant enzyme activity (SOD, CAT, GPx), inflammatory markers (hsCRP, MCP-1, IL-6), muscle damage markers (LDH, CK), cortisol levels, renal function (creatinine), and gene expression patterns through transcriptomic analysis.

The study will include 14 healthy male participants in a randomized, tripple-blind, placebo-controlled, crossover design. Each participant will receive both the ccPT-SIL-NR supplement and placebo for 14 days each, separated by a washout period of at least one week. A high-intensity exercise test will be performed at the end of each supplementation period. Total study duration per participant will be a minimum of 6 weeks.

Detailed description: This study aims to evaluate the effect of a nutritional supplement combining pterostilbene, silybin, and nicotinamide riboside on oxidative stress induced by high-intensity exercise. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species and the body's ability to counteract their harmful effects. High-intensity physical activity is known to increase oxidative stress, potentially leading to cellular damage and inflammation. The supplement under investigation has shown antioxidant properties in preclinical models, and this trial seeks to explore its efficacy in humans. The trial is a randomized, triple-blind, placebo-controlled, and crossover study. Fourteen healthy, physically active men aged 18-50 will be recruited. Each participant will take either the supplement or placebo twice daily for 14 days, followed by a treadmill exercise session at 80% of their VO₂ max. After a washout period, participants will switch treatments and repeat the protocol. Blood and urine samples will be collected both at baseline (prior to supplement intake and without any physical activity) and after the exercise test to evaluate markers of oxidative stress, inflammation, muscle damage, and antioxidant capacity. The main outcome is the change in plasma levels of malondialdehyde (MDA). Secondary outcomes include urinary 8-OHdG and F2-isoprostanes, antioxidant enzyme activities, cortisol levels, and gene expression profiles. This study will help to determine whether the supplement can mitigate exercise-induced oxidative stress and support recovery in recreational athletes.

Participants will attend seven in-person visits:

* V0; week 0 (Screening): Informed consent, eligibility check, medical history, anthropometry.
* V1; week 1 (Baseline 1): Pre-intervention samples collection, supplement/placebo dispensation.
* V2; week 1: Exercise test to determine VO₂ max.
* V3; week 3: First treadmill session after 14 days of intervention with the supplement or placebo, blood draw.
* V4; week 3: Urine sample drop-off post-exercise (0-3h and 3-24h).
* V5; week 4 (Baseline 2): Pre-second intervention samples, crossover begins.
* V6; week 6: Second treadmill session, blood draw.
* V7; week 6: Final urine collection post-exercise (0-3h and 3-24h)..

Eligibility criteria: Inclusion Criteria:

* Male participants between 18 and 50 years of age who are amateur runners.
* Engage in at least 3 continuous running sessions per week, each lasting 60 minutes, which corresponds to a high level of physical activity according to the International Physical Activity Questionnaire (IPAQ).\*
* Self-report being able to continuously run for 45 minutes at high intensity without difficulty.
* Provide signed informed consent prior to participation in the study.
* Able to read, write, and speak either Catalan or Spanish.

  * High level of physical activity according to the IPAQ: vigorous physical activity (such as running) on at least 3 days per week, with a total energy expenditure ≥1500 MET-min/week.

MET value for vigorous activity = 8 × minutes × days per week.

Exclusion Criteria:

* Body Mass Index (BMI) ≤ 18 kg/m² or ≥ 30 kg/m².
* Presence of chronic diseases associated with increased oxidative stress, such as diabetes, hypertension, chronic obstructive pulmonary disease (COPD), or neurodegenerative diseases.
* Personal history of cardiovascular disease, including myocardial infarction, angina pectoris, stroke, or peripheral artery disease.
* Use of antibiotics within 30 days prior to study entry.
* Use of medications or vitamin supplements that may interfere with the study supplement and exceed 100% of the recommended daily intake within 30 days prior to the start of the study.
* Use of polyphenol supplements, herbal extracts, or phytotherapeutic products that may interfere with the study treatment within 30 days prior to study start.
* Alcohol consumption of 4 or more Standard Drink Units (SDUs) per day or 28 SDUs per week.\*

  \*One SDU is defined as 10 grams of alcohol. This corresponds approximately to: 1 glass of wine (120 mL), 1 beer (330 mL), or 1 small spirit (25 mL); 2 SDUs correspond to 1 glass of brandy or liqueur (55 mL), 1 whiskey (70 mL), or a mixed drink (75 mL).
* Active smoker.
* Unintentional weight loss of more than 3 kg in the past 3 months.
* Known food allergies and/or intolerances related to the study products.
* Presence of anemia.
* Presence of chronic gastrointestinal diseases\* or cancer.\*\*

  \*Chronic gastrointestinal diseases include those in an active phase that may interfere with nutrient absorption. Common examples include gastritis, hiatal hernia, Crohn's disease, celiac disease, irritable bowel syndrome, diverticulitis, diverticulosis, chronic constipation, and ulcerative colitis.

  \*\*Individuals with a history of cancer may be included only if they are in complete remission at the start of the study.
* Participation in another drug clinical trial or nutritional intervention study within 30 days prior to study inclusion.
* Inability to follow the study guidelines.

Primary outcomes:
measure: Malondialdehyde (MDA) plasma levels
timeFrame: At week 1, week 3, week 4 and week 6.
Secondary outcomes:
measure: Age
timeFrame: At week 0 (pre-selection visit)
measure: Height (cm)
timeFrame: At week 0 (pre-selection visit)
measure: Body Weight (Kg)
timeFrame: At week 0 (pre-selection visit)
measure: Body Mass Index (BMI) (Kg/m^2)
timeFrame: At week0 (pre-selection visit)
measure: Urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Urine F2-isoprostanes levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Plasma antioxidant capacity
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Erythrocyte Redox Status (GSH/GSSG Ratio)
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Superoxide Dismutase (SOD) Activity
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Catalase (CAT) Activity
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Glutathione Peroxidase (GPx) Activity
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Serum High-Sensitivity C-Reactive Protein (hs-CRP) Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Plasma Monocyte Chemoattractant Protein-1 (MCP-1) Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Plasma Interleukin-6 (IL-6) Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Plasma Lactate Dehydrogenase (LDH) Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Plasma Creatine Kinase (CK) Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Serum Cortisol Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Urinary Creatinine Levels
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Maximal Oxygen Uptake (VO₂ max)
timeFrame: At week 1.
measure: Heart Rate, Treadmill Speed and Incline
timeFrame: At week 1.
measure: Physical Activity Level (Questionnaire-Based)
timeFrame: At week 0, week 1, week 3, week 4 and week 6.
measure: Whole Blood Transcriptomic Profile (RNA-seq)
timeFrame: At week 1, week 3, week 4 and week 6.
measure: Concomitant medication
timeFrame: At week 0, week 1, week 3, week 4 and week 6.
measure: Heart Rate
timeFrame: At week 0, week 1, week 3, week 4 and week 6.
measure: Systolic Blood Pressure
timeFrame: At week 0, week 1, week 3, week 4 and week 6.
measure: Diastolic Blood Pressure
timeFrame: At week 0, week 1, week 3, week 4 and week6.
measure: Use of Dietary Supplements
timeFrame: At week 0, week 1, week 3, week 4 and week 6.
measure: Intervention Compliance (Supplement Intake Adherence)
timeFrame: At week 3 and week 6.
measure: Adverse events
timeFrame: At week 3 and week 6.
Other outcomes:
Locations:
city: Reus
country: Spain
facility: Fundació Eurecat
state: Tarragona
Study officials:
affiliation: Fundació Eurecat
name: Antoni Caimari, PhD
role: PRINCIPAL_INVESTIGATOR
References: