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出境医 / 临床实验 / Ketogenic Diet for Traumatic Brain Injury (KETI)

Ketogenic Diet for Traumatic Brain Injury (KETI)

Study Description
Brief Summary:
Traumatic Brain Injury is a major health concern in United States. There is a un-met need to develop new therapeutic options for faster neuron recovery without causing significant side effects. The role of ketones in neuronal recovery has been studied and has been found to be useful in decreasing size of contusion. The present study aims to study the safety and feasibility profile of ketogenic diet.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Ketogenic Dieting Drug: Ketogenic diet Early Phase 1

Detailed Description:

Traumatic Brain Injury (TBI) is a major health concern for United States contributing nearly one-third of injury-related deaths in United States. The Centers for Disease Control and Prevention (CDC) estimates that 1.7 million people in the United States sustain a TBI each year. It is responsible for significant disabilities and the total cost of productivity loss was estimated to be $76.5 billion in the United States in 2004.

Several animal models have demonstrated the effectiveness of ketones in brain injury to decrease the size of contusion, improving cortical ATP levels, reduced brain edema and cellular apoptosis. Ketones have been shown to be effective in neuromodulation in animal models. Evaluation of carbohydrate free diet has been done in traumatic brain injury patients and it was noted to not cause fluctuations in blood glucose. There is a need for safety and feasibility study of ketogenic diet in traumatic brain injury patients and to understand the effectiveness in neuromodulation in humans. The present study focuses on identifying the safety and feasibility of KD in traumatic brain injury patients.

This pilot project data will be utilized to design future randomized clinical trials. Based on the safety data, further trials will be conducted to evaluate the effectiveness of KD in traumatic brain injury patients and its effectiveness in controlling elevated intracranial pressure. It will open the avenue for consideration of new treatment option for intracranial pressure management and functional recovery. From a nutrition perspective, Ketogenic diet might become the standard of care for this patient population.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Feasibility of Ketogenic Diet for Traumatic Brain Injury Study Protocol
Actual Study Start Date : July 4, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 30, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Subjects on Ketogenic diet
Treatment with KD will consist of 4:1 [fat]: [protein + carbohydrate] weight ratio. KD will be started as soon as the patient is ready for alimentation (while they are in neurocritical care unit). The rate of feeds will be calculated by trained dietician on service. Ketogenic diet will be continued during the entire length of ICU stay. Supplementation with vitamins, calcium and phosphorus will be done.
 Drug: Ketogenic diet
Subjects will be provided with the Ketogenic diet in the form of tube feeds once the decision is made to start the patient on diet.
Other Name: Ketovie
Outcome Measures
Primary Outcome Measures :
  1. Effect of Ketogenic Diet on Intracranial Pressure [ Time Frame: Baseline, till patient on KD (maximim 1 month) ]
    Intracranial Pressure will be measured hourly and it will be trended daily.

  2. Development of Ketosis in blood [ Time Frame: Baseline, till patient on KD ( maximum 1month) ]
    Serum beta-hydroxybutyrate will be done alternate day to assess the level of ketosis in blood.

  3. Ketosis in CSF [ Time Frame: Baseline, till patient on KD (maximum 1 month) ]
    CSF Ketone level will be measured to look for brain ketotic state.

  4. Excretion of Ketones in Urine [ Time Frame: Baseline, till patient on KD (maximum 1 month) ]
    Urine Ketones will be measured alternate day to assess the level of ketosis


Secondary Outcome Measures :
  1. Evaluate change in the neurological exam [ Time Frame: Baseline, before discharge from ICU ]
    Neurological exam will be documented with Glasgow Coma Scale.

  2. Evaluate subjects with gastro-intestinal adverse effects [ Time Frame: Baseline, till patient on KD (Maximum 1month) ]
    Adverse effects like Diarrhea, vomiting, abdominal distension (ileus), abdominal tenderness will be monitored.

  3. Evaluate subjects for abnormal Lipid profile [ Time Frame: Baseline, till patient on KD (Maximum 1month) ]
    Lipid panel will be done weekly to check for alteration in lipid profile while subjects on KD.

  4. Evaluate subjects for muscle wasting [ Time Frame: Baseline, till patient on Kd (Maximum 1month) ]
    Urinary Nitrogen and urinary creatinine will be measured alternate day to look for muscle wasting.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Severe Traumatic Brain Injury
  2. GCS<= 8 with severe head injury
  3. Age more than 18years

Exclusion Criteria:

  1. Diabetic Ketoacidosis
  2. Unstable metabolic condition (persistent hyponatremia, hypernatremia, hypoglycemia, hypocalcemia, acidosis)
  3. Cardiorespiratory or hemodynamic instability
  4. Coagulopathy
  5. Pancreatitis
  6. Liver Failure
  7. Severe hyperlipidemia
  8. Inability to tolerate enteral feeds including ileus
  9. Known Fatty acid oxidation disorder or pyruvate carboxylase deficiency
  10. Any terminally ill patient with poor brain stem reflexes and mortality within 24h of admission.
  11. Pregnant Females
Contacts and Locations

Locations
Layout table for location information
United States, Missouri
University of Missouri Hospital Recruiting
Columbia, Missouri, United States, 65212
Contact: Niraj Arora, MD    573-884-7975 ext 5738829500    arorana@health.missouri.edu   
Contact: Saurabh Kataria, MBBS    5738829500 ext 5738829500      
Sponsors and Collaborators
University of Missouri-Columbia
Tracking Information
First Submitted Date  ICMJE June 3, 2019
First Posted Date  ICMJE June 11, 2019
Last Update Posted Date December 17, 2020
Actual Study Start Date  ICMJE July 4, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Effect of Ketogenic Diet on Intracranial Pressure [ Time Frame: Baseline, till patient on KD (maximim 1 month) ]
    Intracranial Pressure will be measured hourly and it will be trended daily.
  • Development of Ketosis in blood [ Time Frame: Baseline, till patient on KD ( maximum 1month) ]
    Serum beta-hydroxybutyrate will be done alternate day to assess the level of ketosis in blood.
  • Ketosis in CSF [ Time Frame: Baseline, till patient on KD (maximum 1 month) ]
    CSF Ketone level will be measured to look for brain ketotic state.
  • Excretion of Ketones in Urine [ Time Frame: Baseline, till patient on KD (maximum 1 month) ]
    Urine Ketones will be measured alternate day to assess the level of ketosis
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Evaluate change in the neurological exam [ Time Frame: Baseline, before discharge from ICU ]
    Neurological exam will be documented with Glasgow Coma Scale.
  • Evaluate subjects with gastro-intestinal adverse effects [ Time Frame: Baseline, till patient on KD (Maximum 1month) ]
    Adverse effects like Diarrhea, vomiting, abdominal distension (ileus), abdominal tenderness will be monitored.
  • Evaluate subjects for abnormal Lipid profile [ Time Frame: Baseline, till patient on KD (Maximum 1month) ]
    Lipid panel will be done weekly to check for alteration in lipid profile while subjects on KD.
  • Evaluate subjects for muscle wasting [ Time Frame: Baseline, till patient on Kd (Maximum 1month) ]
    Urinary Nitrogen and urinary creatinine will be measured alternate day to look for muscle wasting.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketogenic Diet for Traumatic Brain Injury
Official Title  ICMJE Safety and Feasibility of Ketogenic Diet for Traumatic Brain Injury Study Protocol
Brief Summary Traumatic Brain Injury is a major health concern in United States. There is a un-met need to develop new therapeutic options for faster neuron recovery without causing significant side effects. The role of ketones in neuronal recovery has been studied and has been found to be useful in decreasing size of contusion. The present study aims to study the safety and feasibility profile of ketogenic diet.
Detailed Description

Traumatic Brain Injury (TBI) is a major health concern for United States contributing nearly one-third of injury-related deaths in United States. The Centers for Disease Control and Prevention (CDC) estimates that 1.7 million people in the United States sustain a TBI each year. It is responsible for significant disabilities and the total cost of productivity loss was estimated to be $76.5 billion in the United States in 2004.

Several animal models have demonstrated the effectiveness of ketones in brain injury to decrease the size of contusion, improving cortical ATP levels, reduced brain edema and cellular apoptosis. Ketones have been shown to be effective in neuromodulation in animal models. Evaluation of carbohydrate free diet has been done in traumatic brain injury patients and it was noted to not cause fluctuations in blood glucose. There is a need for safety and feasibility study of ketogenic diet in traumatic brain injury patients and to understand the effectiveness in neuromodulation in humans. The present study focuses on identifying the safety and feasibility of KD in traumatic brain injury patients.

This pilot project data will be utilized to design future randomized clinical trials. Based on the safety data, further trials will be conducted to evaluate the effectiveness of KD in traumatic brain injury patients and its effectiveness in controlling elevated intracranial pressure. It will open the avenue for consideration of new treatment option for intracranial pressure management and functional recovery. From a nutrition perspective, Ketogenic diet might become the standard of care for this patient population.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Traumatic Brain Injury
  • Ketogenic Dieting
Intervention  ICMJE Drug: Ketogenic diet
Subjects will be provided with the Ketogenic diet in the form of tube feeds once the decision is made to start the patient on diet.
Other Name: Ketovie
Study Arms  ICMJE Experimental: Subjects on Ketogenic diet
Treatment with KD will consist of 4:1 [fat]: [protein + carbohydrate] weight ratio. KD will be started as soon as the patient is ready for alimentation (while they are in neurocritical care unit). The rate of feeds will be calculated by trained dietician on service. Ketogenic diet will be continued during the entire length of ICU stay. Supplementation with vitamins, calcium and phosphorus will be done.
Intervention: Drug: Ketogenic diet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 7, 2019) 		10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Severe Traumatic Brain Injury
  2. GCS<= 8 with severe head injury
  3. Age more than 18years

Exclusion Criteria:

  1. Diabetic Ketoacidosis
  2. Unstable metabolic condition (persistent hyponatremia, hypernatremia, hypoglycemia, hypocalcemia, acidosis)
  3. Cardiorespiratory or hemodynamic instability
  4. Coagulopathy
  5. Pancreatitis
  6. Liver Failure
  7. Severe hyperlipidemia
  8. Inability to tolerate enteral feeds including ileus
  9. Known Fatty acid oxidation disorder or pyruvate carboxylase deficiency
  10. Any terminally ill patient with poor brain stem reflexes and mortality within 24h of admission.
  11. Pregnant Females
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982602
Other Study ID Numbers  ICMJE 2014675
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Not yet decided which IPD to share
Responsible Party Niraj Arora, University of Missouri-Columbia
Study Sponsor  ICMJE University of Missouri-Columbia
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Missouri-Columbia
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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