Short-Term Endogenous Hydrogen Sulfide Upregulation
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/30/2018 |
| Start Date: | September 14, 2017 |
| End Date: | June 1, 2018 |
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.
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.
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.
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.
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
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