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Diet Induced Ketosis for Brain Injury - A Feasibility Study

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ClinicalTrials.gov Identifier: NCT04308577
Recruitment Status : Not yet recruiting
First Posted : March 16, 2020
Last Update Posted : March 17, 2020
Sponsor:
Collaborator:
Rigshospitalet, Denmark
Information provided by (Responsible Party):
Jens Rikardt Andersen, University of Copenhagen

Brief Summary:
Each year, approx. 100 patients with severe brain injury is admitted to the Clinic for Neurorehabilitation/TBI Unit, Rigshospitalet. Severe brain injury results in local oxygen deficiency and acid formation in the brain, which together destroys brain cells. The purpose of this study is to investigate whether it is possible to carry out a ketogenic diet therapy for patients with severe brain injury for eight weeks. Ketosis has been shown to be neuroprotective during and after severe brain injury.

Condition or disease Intervention/treatment Phase
Brain Injuries Traumatic Brain Injury Subarachnoid Hemorrhage Apoplexy Anoxic Brain Injury Neuroinfections Other: Ketogenic diet with added MCT Not Applicable

Detailed Description:

Abstract

At the Department of Highly Specialized Neurorehabilitation/Traumatic Brain Injury, Rigshospitalet (satellite department at Hvidovre Hospital), approximately 100 patients (pt.) are admitted with severe brain damage every year. From 2015 to 2017, 305 pt. were admitted. Out of the 305 pt., 162pt. (53%) had traumatic brain injury (TBI), 48pt. (16%) had apoplexy, 35pt. (12%) had other diagnoses (infections, tumors and almost drowning, etc.), 20pt. (7%) had spontaneous subarachnoid hemorrhage (SAH) and 24pt. (8%) had brain damage as a result of cardiac arrest.

TBI is a leading cause of injury-related morbidity and mortality worldwide. According to the Global Burden of Disease Study (2016), there were 27,08 million new cases of TBI globally in 2016. In Denmark, there were 17.302 new cases of TBI in 2016. Clinical studies have repeatedly shown major changes in cerebral energy metabolism after TBI. The secondary brain injury leads to metabolic cellular dysfunction, cerebral edema, and a complex injury cascade. The injury spread includes processes such as inflammation, edema, free radical damage, oxidative damage, ischemic injury, cerebral glucose metabolism disorder, and ion-mediated cell damage. Much of the neurological dysfunction that occurs in acute TBI also occurs in apoplexy, SAH and cerebral ischemia.

A very important adaptive metabolic response after brain injury is the utilization of alternative cerebral energy substrates, including lactate, but also ketone bodies (KB) such as β-hydroxybutyrate (BHB) and acetoacetate (AcAc). In addition to having a central role in the regulation of cerebral energy metabolism after brain injury, KB has other important neuroprotective properties, including attenuation of oxidative stress, apoptotic cell death, and microglial activation. Increasing KB metabolism through fasting or diet-induced ketosis promotes brain resistance to stress and injury, and attenuates acute cerebral injury. Therefore, supplementing with KB, e.g. through the use of a ketogenic diet (KD) with added medium chain fatty acids (MCT), has emerged as a potential non-pharmacological neuroprotective therapy.

KD has been used for many years for the treatment of refractory epilepsy in children and studies done on adults show promising results, but experience from several studies shows major compliance issues. KD has been shown to reduce cerebral edema and apoptosis, as well as improve cerebral metabolism and behavioral outcomes in TBI rodent models, but clinical human trials on adults with TBI are lacking. Apoplexy animal models show positive effects on pathological and functional outcomes of KD intervention or exogenous ketone administration. The only human trial of KD and apoplexy shows that KD is safe and tolerated by patients with acute apoplexy. Our hypothesis is that diet-induced ketosis will reduce the extent of secondary brain damage. The purpose of the trial is to investigate whether an intervention with a ketogenic diet supplemented with MCT is feasible for 8 weeks on hospitalized pt. with severe brain damage. This is the pre-study for a controlled study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Diet Induced Ketosis for Brain Injury - A Feasibility Study: A Ketogenic Diet With MCT Supplementation as a Potential Treatment for Brain Injury in Adults
Estimated Study Start Date : May 15, 2020
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2020

Arm Intervention/treatment
Experimental: Ketogenic diet with MCT
Ketogenic Diet supplemented with MCT everyday for 8 weeks.
Other: Ketogenic diet with added MCT
The intervention is a ketogenic diet consisting of KetoCal 2,5:1 LQ MCT Multi Fibre (Nutricia), Liquigen (MCT)(Nutricia) and ketogenic meals provided by the hospital kitchen. The macronutrient composition of the ketogenic diet given approx.: Protein 11 E%, Carbohydrate 3 E%, Fat 86 E%.




Primary Outcome Measures :
  1. Can the intervention be completed during 8 weeks hospitalization [ Time Frame: 8 weeks ]
    Yes/No, % of intended b-BHB (b-BHB >0,5 mmol/L) ( in % of days

  2. The occurrence of adverse reactions related to the ketogenic treatment, specified [ Time Frame: 8 weeks ]
    5 point scale. 0 = no adverse reaction, 5 = as bad as it can get

  3. Can patients accept the treatment [ Time Frame: 8 weeks ]
    Yes/No, Visual Analog Scale


Secondary Outcome Measures :
  1. Change in Glasgow Coma Scale (GCS) [ Time Frame: 8 weeks ]
    Score 3-15, higher score is better outcome

  2. Change in Early Functional Abilities (EFA) [ Time Frame: 8 weeks ]
    Total score 20-100, higher score is better outcome

  3. Functional Independence Measure (FIM) [ Time Frame: 8 weeks ]
    Change in Total score 18-126, higher score is better outcome

  4. Functional Oral Intake Scale (FOIS) [ Time Frame: 8 weeks ]
    Change in Score 1-7, higher score is better outcome

  5. Ranchos Los Amigos Scale (RLAS) [ Time Frame: 8 weeks ]
    Change in Score 1-8, higher score is better outcome

  6. MRI scan of brain [ Time Frame: 8 weeks ]
    % change in the damaged area



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Ages Eligible for Study:   17 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with severe acquired brain injury (TBI, apoplexy, SAH, anoxic brain injury or neuroinfection)
  • Patients > 17 years
  • Understand and speak Scandinavian language
  • Informed consent from patient or deputy consent if the patient is unable to give consent due to reduced state of consciousness
  • Expectation of prolonged hospitalization

Exclusion Criteria:

  • Contraindication to a ketogenic diet
  • Diabetes mellitus
  • Hypercholesterolemia (statin therapy)
  • Documented arteriosclerotic conditional brain damage
  • At > 10% weight loss during hospitalization after the injury, before pt. transferred to Clinic for Neurorehabilitation/TBI Unit, Rigshospitalet

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04308577


Contacts
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Contact: Maria Edwards, Student +45 41588882 tjv989@alumni.ku.dk
Contact: Jens R Andersen, MD,MPA +45 23346654 jra@nexs.ku.dk

Locations
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Denmark
Clinic of Neurorehabilitation / TBI Unit, Rigshospitalet (Satellite Department on Hvidovre Hospital)
Hvidovre, Denmark, 2650
Contact: Maria Edwards, Student    +45 41588882    tjv989@alumni.ku.dk   
Sub-Investigator: Christian P Hansen, MD, MMT         
Sub-Investigator: Ingrid Poulsen, RN, Ph.D         
Sponsors and Collaborators
Jens Rikardt Andersen
Rigshospitalet, Denmark
Investigators
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Principal Investigator: Maria Edwards, Student University of Copenhagen
Study Director: Jens R Andersen, MD,MPA University of Copenhagen
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Responsible Party: Jens Rikardt Andersen, Associate Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT04308577    
Other Study ID Numbers: U Copenhagen
First Posted: March 16, 2020    Key Record Dates
Last Update Posted: March 17, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Subarachnoid Hemorrhage
Hemorrhage
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases