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Short-Term Endogenous Hydrogen Sulfide Upregulation

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ClinicalTrials.gov Identifier: NCT03303534
Recruitment Status : Completed
First Posted : October 6, 2017
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
C. Keith Ozaki, M.D., F.A.C.S., Brigham and Women's Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carotid Stenosis Caloric Restriction Dietary Supplement: ScandiShake Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 3:2 randomization to short-term protein calorie restriction diet versus regular meals prior to elective carotid artery endarterectomy
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Short-Term Endogenous Hydrogen Sulfide Upregulation
Actual Study Start Date : September 14, 2017
Actual Primary Completion Date : June 1, 2018
Actual Study Completion Date : June 1, 2018

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



Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03303534


Locations
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United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
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Principal Investigator: C. Keith Ozaki, M.D. Brigham and Women's Hospital

Publications:

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Responsible Party: C. Keith Ozaki, M.D., F.A.C.S., Attending Surgeon, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03303534     History of Changes
Other Study ID Numbers: 2016P002507
First Posted: October 6, 2017    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by C. Keith Ozaki, M.D., F.A.C.S., Brigham and Women's Hospital:
inflammation
hydrogen sulfide
caloric restriction
vascular surgery

Additional relevant MeSH terms:
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Carotid Stenosis
Neurotransmitter Agents
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Hydrogen Sulfide
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs