Short-Term Endogenous Hydrogen Sulfide Upregulation

Mass General Brigham

Status: Completed

Conditions: Carotid Stenosis; Caloric Restriction

Treatments: Dietary Supplement: ScandiShake

Study type: Interventional

Funder types: Other

Identifiers

NCT03303534

2016P002507

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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9 participants in 2 patient groups

PCR

Experimental group

Description:

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.

Treatment:

Dietary Supplement: ScandiShake

control regular diet

No Intervention group

Description:

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