Cocoa Flavanols for Modulating Immune Response and Accelerating Recovery

NCT03123068 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 39535
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind, placebo-controlled proof-of-concept clinical trial is intended to demonstrate that preemptive oral administration of cocoa flavanol for five days before surgery will attenuate the surgery-evoked increase of HMGB1 in blood plasma and NFkB signaling in innate immune cells shortly after surgery. A secondary aim is to capture preliminary patient-centered outcomes data and relate these outcomes to the intake of oral cocoa flavanol and surgery-evoked activation of the HMGB1-NFkB signaling axis. Participants will be randomized to receive either an over the counter supplement containing cocoa flavanols, or placebo, for 5 days before surgery.

Conditions

Surgical Recovery

Outcome Measures

Primary Outcomes (1)

• NFkB Signaling in Innate Immune Cells

  Blood samples will be collected to measure possible attenuation of surgery-evoked increase in NFkB signaling in innate immune cells shortly after surgery at specified time points. Phosphorylation of functional markers (activity) was expressed as the arcsinh-transformed value of the median value. Changes in activity over time were captured by building the arcsinh ratio between the arcsinh-value obtained in samples collected at a given time with the arcsinh-value obtained in samples collected at baseline, i.e., before starting the intervention with CocoaVia. Results are reported for NFkB (p65).

  1 hour and 48 hours following surgery

Secondary Outcomes (5)

• HMGB1 Level in Blood Plasma

  1 hour and 48 hours following surgery.

• Step Count Per Minute as a Measure of Functional Recovery - Objective

  post-surgical observation period (6 weeks)

• Days to Mild Impairment as a Measure of Functional Recovery - Subjective

  5 days before surgery though 6 weeks post op.

• Days to Mild Pain as Assessed by WOMAC Pain Scores

  5 days before surgery though 6 weeks post op.

• Days to Half Max Recovery From Fatigue

  5 days before surgery though 6 weeks post op.

Study Arms (2)

Active treatment group - Group A

ACTIVE COMPARATOR

Participants will receive a daily oral dose of 1,000 mg cocoa flavanol (CocoaVia®) for 5 days before surgery. The daily dose will consist of 8 capsules in divided doses throughout the day.

Drug: CocoaVia®

Placebo treatment group - Group B

PLACEBO COMPARATOR

Participants will receive a daily oral dose of a placebo for 5 days before surgery. The daily dose will consist of 8 capsules in divided doses throughout the day.

Other: Placebo

Interventions

CocoaVia® DRUG

CocoaVia® is manufactured by Mars, Inc. It is a dietary supplement of cocoa bean extract, containing 125 mg cocoa flavanols per capsule.

Also known as: Cocoa flavanol

Active treatment group - Group A

Placebo OTHER

The placebo capsules will contain an inert ingredient packaged to be indistinguishable from the active treatment.

Placebo treatment group - Group B

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• Male or female
• Planning to undergo total hip or knee arthroplasty, either primary or revision
• Fluent in English
• Willing and able to sign an informed consent form and HIPAA authorization and to comply with study procedures

You may not qualify if:

• Infectious disease within the last month
• Immune-suppressant therapy within the last 2 months (e.g., azathioprine or cyclosporine)
• Chronic medication with potential immune-modulatory effects (e.g., daily oral morphine-equivalent intake \> 30 mg)
• Major surgery within the last 3 months or minor surgery within the last month.
• History of substance abuse (e.g., alcoholism, drug dependency)
• Pregnancy
• Autoimmune disease interfering with data interpretation (e.g. lupus)
• Renal, hepatic, cardiovascular, or respiratory diseases resulting in clinically relevant impaired function
• Active malignancy
• Participation in another clinical trial of an investigational drug or device within the last month that, in the investigator's opinion, would create an increased risk to the participant or compromise the integrity of the study
• Other conditions compromising a participant's safety or the integrity of the study
• Allergy to active ingredient of CocoaVia®, the study intervention.
• Frequent consumption of dark chocolate and flavanol containing foods (e.g. black tea, red wine, apples)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University Hospital

Stanford, California, 94305, United States

Location

Results Point of Contact

• Title: Professor of Anesthesia
• Organization: Stanford University

ang@stanford.edu

650-723-6412

Study Officials

• Martin S Angst, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo and active treatments will be formulated in identical capsules, and bottled and labeled with coded study numbers that will allow for all parties to remain blinded throughout the data collection phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anethesioloogy, Perioperative and Pain Medicine

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: April 21, 2017
• Study Start: April 17, 2017
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: October 13, 2022
• Results First Posted: November 17, 2021

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)