Black Forest Cocoa Flavanol Supplementation and Health Trial

NCT07747714 | Not Yet Recruiting

• 2 other identifiers: BF-CF-HEALTH-001Pro00092276
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized, double-blind, controlled clinical trial will evaluate the effects of daily cocoa flavanol supplementation on vascular and inflammatory biomarkers in healthy adult men aged 30 to 75 years. Participants will be randomized to receive either a cocoa flavanol supplement or a nutrient-matched low-flavanol control product for 4 to 8 weeks. The study will assess changes in inflammatory biomarkers, endothelial function, oxidative stress markers, vascular measurements, and circulating endothelial progenitor cell-related markers. Optional assessments include flow-mediated dilation and single-cell RNA sequencing of peripheral blood mononuclear cells to explore mechanistic biological responses to cocoa flavanol supplementation.

Conditions

Oxidative Stress; Inflamation; Vascular Health; Endothelial Function

Keywords

Cocoa Flavanols; Flavanol Supplementation; Endothelial Biomarkers; Vascular Function; Endothelial Progenitor Cells; Nitric Oxide; Inflammatory Biomarkers; Pulse Wave Velocity; Flow-Mediated Dilation; Nutrition Study; Dietary Supplement; Healthy Adults

Outcome Measures

Primary Outcomes (15)

• Change From Baseline in Circulating C-Reactive Protein Concentration

  Circulating C-reactive protein will be measured in serum using a custom multiplex bead-based immunoassay. The outcome will be calculated for each participant as the Week 4 concentration minus the baseline concentration. Change from baseline will be compared between the cocoa flavanol supplementation group and the nutrient-matched low-flavanol control group.

  Baseline and Week 4

• Change From Baseline in Circulating Interleukin-6 Concentration

  Circulating interleukin-6 will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Vascular Endothelial Growth Factor A Concentration

  Circulating vascular endothelial growth factor A will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Endothelin-1 Concentration

  Circulating endothelin-1 will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Stromal Cell-Derived Factor 1 Alpha Concentration

  Circulating stromal cell-derived factor 1 alpha, also known as SDF-1α or CXCL12, will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating E-Selectin Concentration

  Circulating E-selectin will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Intercellular Adhesion Molecule-1 Concentration

  Circulating intercellular adhesion molecule-1 will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Vascular Cell Adhesion Molecule-1 Concentration

  Circulating vascular cell adhesion molecule-1 will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating C-C Motif Chemokine Ligand 4 Concentration

  Circulating C-C motif chemokine ligand 4, also known as CCL4, will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating C-C Motif Chemokine Ligand 2 Concentration

  Circulating C-C motif chemokine ligand 2, also known as CCL2, will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Interferon-Gamma Concentration

  Circulating interferon-gamma will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Tumor Necrosis Factor-Alpha Concentration

  Circulating tumor necrosis factor-alpha will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Interleukin-10 Concentration

  Circulating interleukin-10 will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Interleukin-1 Beta Concentration

  Circulating interleukin-1 beta will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

• Change From Baseline in Circulating Leptin Concentration

  Circulating leptin will be measured in serum or plasma using a custom multiplex bead-based immunoassay. The outcome will be calculated as the Week 4 concentration minus the baseline concentration and compared between treatment groups.

  Baseline and Week 4

Secondary Outcomes (2)

• Change From Baseline in Circulating Endothelial Progenitor Cell Frequency

  Baseline and 4 weeks after the first dose

• Change From Baseline in Circulating Nitric Oxide Metabolite Concentration

  Baseline and Week 4

Other Outcomes (2)

• Change From Baseline in Peripheral Blood Mononuclear Cell-Type Abundance by Single-Cell RNA Sequencing

  Baseline and Week 4

• Exploratory Change From Baseline in Single-Cell Gene-Expression Pathway Scores

  Baseline and Week 4

Study Arms (2)

Cocoa Flavanol Supplement

EXPERIMENTAL

Participants will receive a daily cocoa flavanol powder supplement providing approximately 1,200 mg total cocoa flavanols per day for 4 to 8 weeks. The supplement will be administered orally once daily in a blinded fashion.

Dietary Supplement: Cocoa Flavanol Supplement

Low-Flavanol Control

PLACEBO COMPARATOR

Participants will receive a nutrient-matched low-flavanol cocoa-based powder containing less than 2% total flavanols for 4 to 8 weeks. The control product is designed to match the active supplement in appearance and administration while minimizing biologically active flavanol exposure.

Dietary Supplement: Low-Flavanol Control Powder

Interventions

Cocoa Flavanol Supplement DIETARY_SUPPLEMENT

A powdered cocoa flavanol dietary supplement administered orally once daily for 4 to 8 weeks. Each daily serving contains approximately 1,200 mg total cocoa flavanols in a 10 g powder formulation. The supplement is mixed with water or a non-alcoholic beverage and consumed in a blinded fashion.

Also known as: Cocoa Flavanols, CF Supplement

Cocoa Flavanol Supplement

Low-Flavanol Control Powder DIETARY_SUPPLEMENT

A nutrient-matched low-flavanol cocoa-based powder administered orally once daily for 4 to 8 weeks. The control product contains less than 2% total flavanols and is designed to match the active supplement in appearance, taste, and administration while minimizing biologically active flavanol exposure.

Also known as: Control Supplement, Low-Flavanol Cocoa Control

Low-Flavanol Control

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants aged 30 to 75 years.
• Able and willing to provide written informed consent.
• Generally healthy, as determined by medical history and screening assessments.
• Willing and able to comply with all study procedures, including blood collection, daily study-product intake, and required study visits.
• Willing to consume the assigned cocoa flavanol supplement or low-flavanol control product once daily for the duration of the study.
• Willing to provide peripheral blood samples at baseline and at the end of the intervention.
• Willing to maintain generally stable dietary, exercise, sleep, medication, and supplement habits during the study.
• Willing to refrain from initiating new supplements, restrictive diets, fasting regimens, or major exercise programs during the study.
• Not currently taking medications or supplements known to substantially affect vascular function, nitric oxide pathways, inflammation, oxidative stress, or coagulation, unless approved by the investigator.

You may not qualify if:

• Female biological sex.
• Younger than 30 years or older than 75 years.
• Known cardiovascular, metabolic, renal, hepatic, inflammatory, or autoimmune disease, including coronary artery disease, diabetes mellitus, chronic kidney disease, chronic liver disease, rheumatoid arthritis, or another clinically significant inflammatory disorder.
• Hypertension requiring prescription medication.
• Active infection, acute illness, or other clinically significant medical condition at screening or baseline.
• Current use of medications or supplements that may substantially affect vascular function, inflammatory biomarkers, nitric oxide pathways, oxidative stress, or coagulation, including chronic nonsteroidal anti-inflammatory drugs, systemic corticosteroids, anticoagulants, antiplatelet drugs, prescription immunomodulatory agents, phosphodiesterase-5 inhibitors, or high-dose antioxidant supplements, unless approved by the investigator.
• Known allergy, hypersensitivity, or intolerance to cocoa, chocolate, cocoa flavanols, or any ingredient in either study product.
• Gastrointestinal disease or condition that may interfere with digestion or absorption of the study product, including celiac disease, inflammatory bowel disease, active gastritis, or a clinically significant malabsorption disorder.
• Current smoking or vaping of nicotine or cannabis products.
• Major psychiatric illness, cognitive impairment, or another condition that may interfere with informed consent, adherence, or completion of study procedures.
• Alcohol or drug abuse within the previous 12 months that, in the investigator's judgment, may affect participant safety or study adherence.
• Participation in another interventional clinical study within 30 days before screening.
• Plans to begin a new medication, supplement, restrictive diet, fasting regimen, or major exercise program during the study period.
• Any condition or circumstance that, in the investigator's judgment, would increase participant risk, interfere with study procedures, compromise adherence, or affect interpretation of the study results.

Sponsors & Collaborators

• The Black Forest LLC: lead

Study Sites (2)

Black Forest Supplements (The Black Forest LLC)

Miami, Florida, 33166, United States

Location

Power Wellness Spot

Miami, Florida, 33166, United States

Location

Study Officials

• Shlomi Brielle, PhD

  The Black Forest LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shlomi Brielle, PhD

CONTACT

‪(617) 744-9534‬; briellescientific@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, care providers, and outcome assessors are blinded to treatment allocation. Study products are packaged in identical coded containers to maintain masking.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomized 1:1 to receive either Cocoa Flavanol supplementation or a nutrient-matched low-flavanol control product for 4-8 weeks in a double-blind parallel-group design.

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 5, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)