Short-Term Endogenous Hydrogen Sulfide Upregulation

June 27, 2018 updated by: C. Keith Ozaki, M.D., F.A.C.S., Brigham and Women's Hospital
This research study will compare the impact of dietary restriction pre-operatively before carotid endarterectomy compared to the standard nutrition that a patient typically eats. The investigators want to find out how patients comply and generally how well patients do with this type of dietary restriction before their surgery since animal studies suggest that short - term dietary restriction may be beneficial before surgery.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The primary, scientific long term objective is to study any correlation that brief upregulation of endogenous hydrogen sulfide (H2S) via pre-operative protein calorie restriction (PCR) in elective major surgery may have biologic effects in humans. In this study, the investigators plan to evaluate patient compliance and the physiologic response pre-operative PCR has on patients undergoing carotid endarterectomy surgery. This will be explored via two primary aims.

The First Aim looks to create a prospective, fast-track, one-year study of 40 vascular surgery patients undergoing elective carotid artery endarterectomy randomized into two pre-operative dietary groups: observational group (n=16) and PCR (commercially available ScandiShake x 3 days, n=24). This pilot study is based on preliminary data balanced with economic and clinical feasibility considerations. The primary endpoints of this study are: 1) feasibility of subject compliance with PCR (measured by direct dietary intake data and serum markers including plasma free amino acids and insulin-like growth factor; thus the 2:3 randomization) and 2) measurement of H2S and standard markers of stress before and after surgery (including stress hormones, oxidative stress, inflammation and cardiac troponin T levels). Individual patient's microbiomes,phenotype of circulating blood cells, adipose tissue (peri-vascular, subcutaneous), and the excised carotid plaque will be characterized to inform on potential mechanistic links among these and PCR induced H2S upregulation, reduced peri-operative stress, atherosclerotic plaque stability, and improved outcome (baseline and peri-procedural clinical datasets will be completed) for future clinical trials. Key secondary data points include observing endpoints such as carotid restenosis and surgical complications (cardiac, neurologic, wound, etc) between the two groups, which the investigators hypothesize will help to inform future trials. This pilot study will elucidate not only the practicality of pre-operative short term dietary restriction, but also provide physiologic data to support the long term primary scientific objective stated previously.

The Second Specific Aim is to establish a robust human discovery multi-institutional platform to capitalize on multiple aspects of this carefully constructed initiative toward long-term goals such as better understanding and translation of the biologic mechanisms of H2S and PCR. Data collected in the first aim across institutions will be integrated and made public.This platform will encourage communication and collaboration among basic scientists, translational investigators, and clinical communities. This synergy will allow the investigators to define the mechanisms of H2S and PCR effects, and will also give insights into the human response to trauma (lipidomics, microbiome, proteins/microRNAs) that regulate the pro-inflammatory response to injury, and will allow for mechanistic links among these factors ties to surgical outcomes.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • consenting adults (men and women)
  • clinical indication for carotid endarterectomy (CEA) as determined by attending vascular surgeon
  • if symptomatic, patients must be able to safely have surgery timed for PCR intervention

Exclusion Criteria:

  • intolerance or allergy to any ingredients in the PCR diet (ScandiShake ingredients or almond milk/nuts)
  • active infection
  • pregnancy
  • malnutrition determined by serum albumin lower than BWH reference value of 3.5 g/dL
  • active drug dependency or alcoholism that could interfere with protocol adherence
  • active non-cutaneous cancer under treatment with chemotherapeutic

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PCR
pre-operative protein calorie restricted (PCR) group. participants randomized to this arm will consume scandishake diet (strawberry, caramel, banana cream, vanilla) mixed with almond milk for three days inpatient prior to planned elective carotid endarterectomy. Water is ad libitum for this cohort. Nutritionists will prepare shakes so participants will achieve 30% calorie restriction and severe protein restriction during the three days on the diet.
Dietary supplement: ScandiShake
weight gain supplement low in protein
NO_INTERVENTION: control regular diet
participants in this cohort are randomized to the control group and will have no dietary restriction three days in patient prior to planned elective carotid endarterectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
subject compliance with PCR
Time Frame: three days pre-operatively
will measure subject compliance via direct dietary intake data by way of written food diary and biologic markers (serum markers including plasma free amino acids and insulin-like growth factor).
three days pre-operatively

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
measurement of local and systemic hydrogen sulfide and standard markers of stress peri-procedurally
Time Frame: change over 4.5 weeks from baseline
hydrogen sulfide upregulation has been linked to improved vascular surgery outcomes in rodent models when rodents are pre-operatively on PCR diets
change over 4.5 weeks from baseline
fecal microbiome characterization
Time Frame: change over 4.5 weeks from baseline
if PCR and surgery has an impact on patient microbiome or microbiome related metabolites
change over 4.5 weeks from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: C. Keith Ozaki, M.D., Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 14, 2017

Primary Completion (ACTUAL)

June 1, 2018

Study Completion (ACTUAL)

June 1, 2018

Study Registration Dates

First Submitted

September 27, 2017

First Submitted That Met QC Criteria

October 2, 2017

First Posted (ACTUAL)

October 6, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 28, 2018

Last Update Submitted That Met QC Criteria

June 27, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016P002507

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carotid Stenosis

Clinical Trials on ScandiShake

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe