Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03303534
Other study ID # 2016P002507
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date September 14, 2017
Est. completion date June 1, 2018

Study information

Verified date June 2018
Source Brigham and Women's Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 9
Est. completion date June 1, 2018
Est. primary completion date June 1, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
ScandiShake
weight gain supplement low in protein

Locations

Country Name City State
United States Brigham and Women's Hospital Boston Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (8)

Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Treviño-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell. 2015 Jan 15;160(1-2):132-44. doi: 10.1016/j.cell.2014.11.048. Epub 2014 Dec 23. — View Citation

Hine C, Kim HJ, Zhu Y, Harputlugil E, Longchamp A, Matos MS, Ramadoss P, Bauerle K, Brace L, Asara JM, Ozaki CK, Cheng SY, Singha S, Ahn KH, Kimmelman A, Fisher FM, Pissios P, Withers DJ, Selman C, Wang R, Yen K, Longo VD, Cohen P, Bartke A, Kopchick JJ, Miller R, Hollenberg AN, Mitchell JR. Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production. Cell Metab. 2017 Jun 6;25(6):1320-1333.e5. doi: 10.1016/j.cmet.2017.05.003. — View Citation

Longchamp A, Harputlugil E, Corpataux JM, Ozaki CK, Mitchell JR. Is Overnight Fasting before Surgery Too Much or Not Enough? How Basic Aging Research Can Guide Preoperative Nutritional Recommendations to Improve Surgical Outcomes: A Mini-Review. Gerontology. 2017;63(3):228-237. doi: 10.1159/000453109. Epub 2017 Jan 5. Review. — View Citation

Longchamp A, Tao M, Bartelt A, Ding K, Lynch L, Hine C, Corpataux JM, Kristal BS, Mitchell JR, Ozaki CK. Surgical injury induces local and distant adipose tissue browning. Adipocyte. 2015 Nov 20;5(2):163-74. doi: 10.1080/21623945.2015.1111971. eCollection 2016 Apr-Jun. — View Citation

Mauro CR, Tao M, Yu P, Treviño-Villerreal JH, Longchamp A, Kristal BS, Ozaki CK, Mitchell JR. Preoperative dietary restriction reduces intimal hyperplasia and protects from ischemia-reperfusion injury. J Vasc Surg. 2016 Feb;63(2):500-9.e1. doi: 10.1016/j.jvs.2014.07.004. Epub 2014 Aug 8. — View Citation

Mitchell JR, Beckman JA, Nguyen LL, Ozaki CK. Reducing elective vascular surgery perioperative risk with brief preoperative dietary restriction. Surgery. 2013 Apr;153(4):594-8. doi: 10.1016/j.surg.2012.09.007. Epub 2012 Dec 4. Review. — View Citation

Nguyen B, Tao M, Yu P, Mauro C, Seidman MA, Wang YE, Mitchell J, Ozaki CK. Preoperative diet impacts the adipose tissue response to surgical trauma. Surgery. 2013 Apr;153(4):584-93. doi: 10.1016/j.surg.2012.11.001. Epub 2012 Dec 27. — View Citation

Robertson LT, Treviño-Villarreal JH, Mejia P, Grondin Y, Harputlugil E, Hine C, Vargas D, Zheng H, Ozaki CK, Kristal BS, Simpson SJ, Mitchell JR. Protein and Calorie Restriction Contribute Additively to Protection from Renal Ischemia Reperfusion Injury Partly via Leptin Reduction in Male Mice. J Nutr. 2015 Aug;145(8):1717-27. doi: 10.3945/jn.114.199380. Epub 2015 Jun 3. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary subject compliance with PCR 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 measurement of local and systemic hydrogen sulfide and standard markers of stress peri-procedurally 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
Secondary fecal microbiome characterization if PCR and surgery has an impact on patient microbiome or microbiome related metabolites change over 4.5 weeks from baseline
See also
  Status Clinical Trial Phase
Recruiting NCT03631381 - Retrospective Study of Carotid Surgery in Dijon
Completed NCT05437991 - Ultrasonographic Morphology Assessment of Low-grade Carotid Stenosis N/A
Completed NCT02722720 - Carotid Arteries Stenting Complications: Transradial Approach Versus Transfemoral N/A
Completed NCT02336958 - Ultrasound Guided Intermediate Cervical Plexus Block and Additional Perivascular Local Anesthetic Infiltration N/A
Completed NCT02630862 - Oxidative Stress and Oxysterols Profiling in Patients With Carotid Revascularization N/A
Completed NCT00536796 - Percentage of Secondary Prevention Patients Treated to Their LDL-C Targets N/A
Recruiting NCT05566301 - Multicentric Study on Clopidogrel Resistance in DAPT for CAS (MULTI-RESCLOSA)
Completed NCT01480206 - Overlay of 3D Scans on Live Fluoroscopy for Endovascular Procedures in the Hybrid OR
Recruiting NCT05250349 - TRAnscranial Doppler CErebral Blood Flow and Cognitive IMPAIRment in Heart Failure
Recruiting NCT05845710 - Direct Access Carotid Artery Stenting Using the Neuroguard IEP System (PERFORMANCE III) N/A
Recruiting NCT01732523 - Predictive Value of Neovascularization Within Asymptomatic Carotis Stenosis on CEUS
Completed NCT01315288 - A Randomized Trial of Clinical Decision Making in Asymptomatic Carotid Stenosis N/A
Withdrawn NCT00401921 - A Study of the Effects of Minocycline on Cognitive Function After Carotid Endarterectomy Phase 2
Recruiting NCT01273350 - A Prospective, Non-Randomized, Evaluation of Low-Risk Patients Undergoing Carotid Stenting With ANgiomax (Bivalirudin) N/A
Completed NCT03215550 - PET-MRI Imaging in Patients With Symptomatic Carotid Artery Stenosis
Completed NCT03215563 - PET-MRI Imaging in Patients With Acute Neurovascular Syndrome
Completed NCT04553549 - Safety and Feasibility of the Infinity Catheter for Radial Access
Completed NCT03596229 - Major Adverse Cardiac Events After Carotid Endarterectomy
Completed NCT04255316 - Modified Method of Eversion Carotid Endarterectomy in Patients With Extensive Atherosclerotic Disease of Carotid Bifurcation N/A
Completed NCT03410576 - Perioperative Time Course of MMP-9 and Its Inhibitor During Carotid Artery Stenting and Carotid Endarterectomy N/A