Brain InjuriesNCT04308577
Diet Induced Ketosis for Brain Injury - A Feasibility Study
A study testing Ketogenic diet with added MCT in people with Brain Injuries and Traumatic Brain Injury, run by Jens Rikardt Andersen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injuries, Traumatic Brain Injury, Subarachnoid Hemorrhage
- What is being tested?
- Ketogenic diet with added MCT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Oct 2020to 31 May 2021
- 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
- Diagnosed with severe acquired brain injury (TBI, stroke, SAH, anoxic brain injury or neuroinfection)
- Patients ≥ 18 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
Who cannot join
- Contraindication to a ketogenic diet
- Dysregulated Diabetes Mellitus
- Medicated for elevated triglycerides
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Clinic of Neurorehabilitation / TBI Unit, Rigshospitalet (Satellite Department on Hvidovre Hospital)
Hvidovre, 2650
About this study
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
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 six weeks. Ketosis has been shown to be neuroprotective during and after severe brain injury.
Read the 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 6 weeks on hospitalized pt. with severe brain damage. This is the pre-study for a controlled study.
- Conditions
- Brain Injuries, Traumatic Brain Injury, Subarachnoid Hemorrhage, Stroke, Anoxic Brain Injury, Neuroinfections
- Being tested
- Ketogenic diet with added MCT
- Medical subject headings
- Brain Injuries, Brain Injuries, Traumatic, Subarachnoid Hemorrhage, Stroke, Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic diet with added MCTOther
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%.
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic diet with MCT | Experimental | Ketogenic Diet supplemented with MCT everyday for 6 weeks. Receives: Other: Ketogenic diet with added MCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Can the intervention be completed during 6 weeks hospitalization
Yes/No, % of patients with intended b-BHB (b-BHB ≥ 0,5 mmol/L) in % of intervention days
Measured: 6 weeks
The occurrence of adverse reactions related to the ketogenic treatment, specified
% of days with adverse effects during intervention
Measured: 6 weeks
Can patients accept the treatment
Yes/No, % of intervention days
Measured: 6 weeks
Secondary outcomes (5)
Change in Glasgow Coma Scale (GCS)
Score 3-15, higher score is better outcome
Measured: 6 weeks
Change in Early Functional Abilities (EFA)
Total score 20-100, higher score is better outcome
Measured: 6 weeks
Change in Functional Independence Measure (FIM)
Change in Total score 18-126, higher score is better outcome
Measured: 6 weeks
Change in Functional Oral Intake Scale (FOIS)
Change in Score 1-7, higher score is better outcome
Measured: 6 weeks
Change in Ranchos Los Amigos Scale (RLAS)
Change in Score 1-8, higher score is better outcome
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start5 Oct 2020
- Primary completion9 Feb 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jens Rikardt Andersen
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor-investigator, Jens Rikardt Andersen, University of Copenhagen
- Investigators
- Maria Edwards, Student, Principal investigator, University of CopenhagenJens R Andersen, MD,MPA, Study director, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308577
- Sponsor's protocol ID
- U Copenhagen
- Status last verified
- Jul 2021
- First submitted
- 6 Mar 2020
- Last updated
- 15 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Edwards MGP, Andersen JR, Curtis DJ, Riberholt CG, Poulsen I. Diet-induced ketosis in adult patients with subacute acquired brain injury: a feasibility study. Front Med (Lausanne). 2024 Mar 19;10:1305888. doi: 10.3389/fmed.2023.1305888. eCollection 2023.
PubMed 38571572
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04308577
- Acronym / sponsor ID
- U Copenhagen
- Conditions
- Brain Injuries, Traumatic Brain Injury, Subarachnoid Hemorrhage, Stroke, Anoxic Brain Injury, Neuroinfections
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Jens Rikardt AndersenUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 9 Feb 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 16 Mar 2020 (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.
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 six weeks. Ketosis has been shown to be neuroprotective during and after severe brain injury.
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 6 weeks on hospitalized pt. with severe brain damage. This is the pre-study for a controlled study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketogenic diet with MCT | Experimental | Other: Ketogenic diet with added MCTKetogenic Diet supplemented with MCT everyday for 6 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with severe acquired brain injury (TBI, stroke, SAH, anoxic brain injury or neuroinfection)
- Patients ≥ 18 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
Key exclusion criteria (3 listed)
- Contraindication to a ketogenic diet
- Dysregulated Diabetes Mellitus
- Medicated for elevated triglycerides
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 |
|---|---|---|
| Ketogenic diet with added MCTThe 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%. | Other | Ketogenic diet with MCT |
Primary outcome
Can the intervention be completed during 6 weeks hospitalization
Time frame: 6 weeks
Yes/No, % of patients with intended b-BHB (b-BHB ≥ 0,5 mmol/L) in % of intervention days
The occurrence of adverse reactions related to the ketogenic treatment, specified
Time frame: 6 weeks
% of days with adverse effects during intervention
Can patients accept the treatment
Time frame: 6 weeks
Yes/No, % of intervention days
5 secondary outcomes
Change in Glasgow Coma Scale (GCS)
Time frame: 6 weeks
Change in Early Functional Abilities (EFA)
Time frame: 6 weeks
Change in Functional Independence Measure (FIM)
Time frame: 6 weeks
Change in Functional Oral Intake Scale (FOIS)
Time frame: 6 weeks
Change in Ranchos Los Amigos Scale (RLAS)
Time frame: 6 weeks
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 15 Jul 2021.
- Derived from this study: PubMed 38571572Edwards MGP, Andersen JR, Curtis DJ, Riberholt CG, Poulsen I. Diet-induced ketosis in adult patients with subacute acquired brain injury: a feasibility study. Front Med (Lausanne). 2024 Mar 19;10:1305888. doi: 10.3389/fmed.2023.1305888. eCollection 2023.
- Individual participant dataSharing planned: No
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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.
Maria Edwards, Student principal investigator
University of Copenhagen
Jens R Andersen, MD,MPA study director
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic diet with added MCT in people with Brain Injuries and Traumatic Brain Injury, run by Jens Rikardt Andersen at 1 site in Denmark.
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 5 inclusion and 3 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 15 Jul 2021. 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 Denmark. 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?
Can the intervention be completed during 6 weeks hospitalization (time frame: 6 weeks). The study lists 3 primary outcomes in all. 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 NCT04308577, which also lists 1 linked publication.
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 15 Jul 2021.