Short-Term Endogenous Hydrogen Sulfide Upregulation For Vein Graft Disease

NCT05457881 | Withdrawn

• 1 other identifier: 2021P002206
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized, controlled trial to evaluate patient compliance and biologic mechanisms of a short-term pre-operative Protein-Calorie Restriction (PCR) diet in comparison to a normal ad libitum diet for 4 days before elective vascular surgery involving a major operation. After a pilot study exploring the safety and feasibility of the PCR diet conducted inpatient before carotid endarterectomy titled Short-Term Endogenous Hydrogen Sulfide Upregulation, and a follow-up study titled Dietary Restriction in Vascular Surgery, the investigators now aim to expand the study to at home diet among a variety of vascular surgery procedures. This study will further elucidate not only the practicality of pre-operative short term dietary restriction, but also provide early data to inform biologic mechanisms and to inform future efficacy trails.

Conditions

Vascular Diseases; Surgery

Outcome Measures

Primary Outcomes (6)

• Compliance with outpatient Protein-Calorie Restriction measured via food diary

  Subject compliance with PCR will be measured through direct dietary intake data via food diary in comparison to the ad libitum diet. But one of the indirect goals of the initiative is to better understand how compliance can be assessed in this population.

  1 Month

• Compliance with outpatient Protein-Calorie Restriction measured via biologic assays for plasma free amino acids

  Subject compliance with PCR will be measured through biologic assays (e.g., plasma free amino acids) in comparison to the ad libitum diet. But one of the indirect goals of the initiative is to better understand how compliance can be assessed in this population.

  1 Month

• Compliance with outpatient Protein-Calorie Restriction measured via biologic assays for pre-albumin

  Subject compliance with PCR will be measured through biologic assays (e.g., insulin-like growth factor) in comparison to the ad libitum diet. But one of the indirect goals of the initiative is to better understand how compliance can be assessed in this population.

  1 Month

• Compliance with outpatient Protein-Calorie Restriction measured via biologic assays insulin-like growth factor

  Subject compliance with PCR will be measured through direct dietary intake data via food diary, and we will also have biologic assays for serum markers including plasma free amino acids, pre-albumin, and insulin-like growth factor in comparison to the ad libitum diet. But, one of the indirect goals of the initiative is to better understand how compliance can be assessed in this population.

  1 Month

• Change over time from baseline values to values before surgery and day 1 after surgery in the comparison of H2S and standard biological markers of stress in blood

  H2S and standard biological markers of stress are collected at baseline, immediately before surgery, and day 1 after surgery. Biological markers include: adipose phenotyping (quantification of adipokines, adipose derived hormones), leukocyte phenotyping and quantification via flow cytometry, and serum assays of IL-1beta, IL-6, IL-8, HGF, leptin, MCP-1, PAI-1, resistin, NGF, TNF, adiponectin, hydrogen sulfide (including production capacity) assays, insulin, lipid panels, FGF 21, pre-albumin, epinephrine, norepinephrine, dopamine, CBC with differential, basic metabolic panel including calcium. These biomarkers will be quantified in the various tissues for individual participants and be mathematically aggregated for groups (i.e., an aggregate unit of measurement will be used)"

  Baseline, Day 0, Day 1

• Major Adverse Limb Event

  Untreated loss of conduit patency and/or severe limb ischemia leading to an intervention or major amputation. Includes acute limb ischemia (including the need for thrombectomy/ thrombolysis), major amputation (above the ankle), need for re-do surgical revascularization for the index limb.

  2 years

Secondary Outcomes (4)

• Comparison of surgical and medical complications

  1 Month

• One-year survival

  1 year

• Renal dysfunction, stroke, myocardial infarction, patency of the vein graft (primary, primary assisted, secondary), survival.

  1 Month, 1 year

• Wound Complication

  1 Month

Other Outcomes (2)

• Gut microbiome Analysis

  0-34 days

• Microbiome-derived circulating metabolites

  0-34 days

Study Arms (2)

Protein-calorie restriction

EXPERIMENTAL

Four day dietary intervention immediately before surgery of Scandi-Shake \[any of 4 flavors - vanilla, strawberry, banana cream, and caramel\] mixed with almond milk (85 grams Scandi-Shake mix to 240 cc almond milk) calculated individually for a total daily volume to achieve 30% caloric restriction and 70% protein restriction, based on gender, age, height, weight, and activity level.

Dietary Supplement: Scandi-Shake

Control

NO INTERVENTION

Ad libitum diet for four days immediately before surgery

Interventions

Scandi-Shake DIETARY_SUPPLEMENT

Scandi-Shake \[any of 4 flavors - vanilla, strawberry, banana cream, and caramel\] mixed with almond milk (85 grams Scandi-Shake mix to 240 cc almond milk), calculated individually for a total daily volume to achieve 30% caloric restriction and 70% protein restriction, based on ideal body weight. The Mifflin St. Jeor equation will be used to calculate the total 24-hour energy needs based on gender, age, height, weight, and activity factor for the PCR diet. Daily physical activity will be assessed by questionnaire to determine the activity factor for accurate calorie restriction calculations. Nutritionists will use this equation to create a unique shake for each individual patient. The shakes will be separated into 4 equal portions per day, for a total of 16 portions across the 4 pre-operative days. Patients can consume the 4 daily portions at whichever time of day they choose. The shakes are frozen 24 hours before distribution.

Protein-calorie restriction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• Patients planned for non-emergency lower extremity vein bypass surgery
• Projected survival of at least one year
• Ability to provide informed consent
• Albumin ≥3.0 and negative pregnancy test (if relevant)
• No known allergy to Scandi-Shake ingredients

You may not qualify if:

• \<18 years of age
• Emergency lower extremity vascular surgery
• Projected survival of \< one year
• Albumin \<3.0
• Pregnancy, intention to become pregnant, or lack of standard contraception method
• Allergy to Scandi-Shake ingredients

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

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MeSH Terms

Conditions

Vascular Diseases

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Study Officials

• Charles K Ozaki, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be discretely randomized by the clinical research assistants upon final clearance for their procedure by the anesthesiology service, and their assigned group will be concealed to all subsequent team members (clinicians, research scientists, statistician) until data lock
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: John A. Mannick Professor of Surgery

Model Details: 3:2 randomization to short-term protein calorie restriction diet versus regular meals prior to elective major vascular surgery

Study Record Dates

• First Submitted: February 7, 2022
• First Posted: July 14, 2022
• Study Start: March 1, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)