Carotid StenosisNCT03303534
Short-Term Endogenous Hydrogen Sulfide Upregulation
A study testing ScandiShake in people with Carotid Stenosis and Caloric Restriction, run by Brigham and Women's Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carotid Stenosis, Caloric Restriction
- What is being tested?
- ScandiShake
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2017to 1 Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- Carotid Stenosis, Caloric Restriction
- Being tested
- ScandiShake
- Keywords
- inflammation, hydrogen sulfide, caloric restriction, vascular surgery
- Medical subject headings
- Carotid Stenosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ScandiShakeDietary supplement
weight gain supplement low in protein
| Study group | Role | What they receive |
|---|---|---|
| PCR | Experimental | 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. Receives: Dietary Supplement: ScandiShake |
| control regular diet | No intervention | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: three days pre-operatively
Secondary outcomes (2)
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
Measured: change over 4.5 weeks from baseline
fecal microbiome characterization
if PCR and surgery has an impact on patient microbiome or microbiome related metabolites
Measured: change over 4.5 weeks from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2017
- Study start14 Sep 2017
- Primary completion1 Jun 2018
- Study completion1 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Carotid StenosisStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, C. Keith Ozaki, M.D., F.A.C.S., Brigham and Women's Hospital
- Investigators
- C. Keith Ozaki, M.D., Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03303534
- Sponsor's protocol ID
- 2016P002507
- Status last verified
- Jun 2018
- First submitted
- 27 Sep 2017
- Last updated
- 28 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28591635Longchamp 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.
PubMed 28052287Longchamp 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.
PubMed 27386152Robertson LT, Trevino-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.
PubMed 26041674Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Trevino-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.
PubMed 25542313Mauro CR, Tao M, Yu P, Trevino-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.
PubMed 25124359Nguyen 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.
PubMed 23274098Mitchell 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.
PubMed 23218877
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-Term Endogenous Hydrogen Sulfide Upregulation
- ClinicalTrials.gov ID
- NCT03303534
- Acronym / sponsor ID
- 2016P002507
- Conditions
- Carotid Stenosis, Caloric Restriction
- Keywords
- inflammation, hydrogen sulfide, caloric restriction, vascular surgery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 14 Sep 2017 (actual)
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 1 Jun 2018 (actual)
- First posted
- 6 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 3:2 randomization to short-term protein calorie restriction diet versus regular meals prior to elective carotid artery endarterectomy
| Arm | Type | Receives |
|---|---|---|
| PCR | Experimental | Dietary Supplement: ScandiShakepre-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. |
| control regular diet | No intervention | –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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ScandiShakeweight gain supplement low in protein | Dietary supplement | PCR |
Primary outcome
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).
2 secondary outcomes
measurement of local and systemic hydrogen sulfide and standard markers of stress peri-procedurally
Time frame: change over 4.5 weeks from baseline
fecal microbiome characterization
Time frame: change over 4.5 weeks from baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
- Background: PubMed 28591635Hine 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.
- Background: PubMed 28052287Longchamp 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.
- Background: PubMed 27386152Longchamp 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.
- Background: PubMed 26041674Robertson LT, Trevino-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.
- Background: PubMed 25542313Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Trevino-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.
- Background: PubMed 25124359Mauro CR, Tao M, Yu P, Trevino-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.
- Background: PubMed 23274098Nguyen 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.
- Background: PubMed 23218877Mitchell 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.
- Individual participant dataSharing planned: No
Related trials for Carotid Stenosis
Not yet recruitingObservational study
Vascular Health and Function in Cystic Fibrosis
Cystic Fibrosis, Endothelial Dysfunction
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruiting
Optical Coherence Tomography-Assisted Strategy for Interventional Management of Symptomatic Carotid Stenosis (OASIS-C)
Carotid Stenosis
Not yet recruitingObservational study
A First-in-Human Feasibility Study of the Vibrant Stroke Detection Technology During Carotid Endarterectomies
Carotid Stenosis
RecruitingObservational study
Perioperative GFAP and Neurological Complications After Carotid Endarterectomy
Carotid Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C. Keith Ozaki, M.D. principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ScandiShake in people with Carotid Stenosis and Caloric Restriction, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
subject compliance with PCR (time frame: three days pre-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03303534, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2018.