Effects of a Ketogenic Diet on Acute Stroke

Study Overview
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Brief Summary
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The purpose of this controlled, randomized intervention is to investigate whether a fat-based (ketogenic) diet given for a week has a positive effect on blood sugar, mortality and function in patients hospitalized with acute stroke compared to the effect of a usual diet. The study hypothesis is that a ketogenic diet and reduced availability of glucose to the brain cells will reduce the volume of neuronal damage in the brain and improve function. The intervention will take place at the neurological units of Glostrup and Bispebjerg Hospital in Denmark.

Detailed Description
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A ketogenic diet can induce ketosis after a period of 2-3 days and offer the brain an alternative energy substrate to glucose in the form of ketone bodies. Feeding the brain ketone bodies can potentially benefit a stroke patient's brain in several ways: Stroke is characterized by impaired blood and oxygen supply to brain cells. This can cause glucose to convert to lactate which is toxic for the brain. Decreasing glucose availability to brain cells may thus potentially decrease the area of damage in the ischemic penumbra (perifephery of the stroke). Compared with sugar, burning ketone bodies requires less oxygen to produce the same amount of energy, suggesting that brain cells could have a potential greater chance of surviving during circumstances of reduced oxygen supply. By decreasing mitochondria activity, ROS synthesis is also decreased, which can help decrease the necrotic area around the ischemic penumbra. Furthermore, the ketogenic diet does not induce an increase in blood sugar which could be an advantage since many stroke patients are admitted with hyperglycemia associated with a worse outcome.

Official Title
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The Effect of a Ketogenic Diet on Blood Glucose, Function and Disease Progress in Acute Stroke Patients

Conditions
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Acute Stroke

Intervention / Treatment
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* Dietary Supplement: Ketocal 4:1 (Nutricia)
* Dietary Supplement: Control diet: Regular diet offered at the hospitals
* Dietary Supplement: Ketogenic meals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ischemic or hemorrhagic stroke. NIHSS score of at least 5. Both primary and recurrent cases. Inclusion as early as possible, but no later than 72 hours from symptom onset. Patients with expected hospitalization for a minimum of seven days. Adult patients with cognitive ability to give informed consent. Patients with writing and orally accepted participation. Exclusion Criteria: Patients with SAH and traumatic hematoma. Patients with pancreatic insufficiency (steatorrhea). Patients unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic diet<br>Acute stroke patients will receive a ketogenic diet (Ketocal 4:1 and ketogenic meals) for the first week after inclusion | Dietary Supplement: Ketocal 4:1 (Nutricia)<br> <br> Dietary Supplement: Ketogenic meals<br> <br> |
| Active Comparator: Control diet<br>Acute stroke patients will receive a control diet (the regular diet, enteral or oral, offered at the hospitals) for the first week after inclusion. | Dietary Supplement: Control diet: Regular diet offered at the hospitals<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline NIHSS (national institute of health stroke scale) at 90 days | NIHSS is a common stroke scale used to objectively quantify the impairment caused by a stroke | Baseline and 90 days | 
| Change from baseline fasting blood sugar at 7 days |  | Baseline and 7 days | 
| Change from baseline p-C-peptide at 7 days |  | Baseline and 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline p-triglyceride (fasting) at 7 days |  | Baseline and 7 days | 
| Change from baseline p-LDL at 7 days |  | Baseline and 7 days | 
| Change from baseline p-CRP at 7 days |  | Baseline and 7 days | 
| Change from baseline p-beta-hydroxy butyrate at 7 days |  | Baseline and 7 days | 
| Change from baseline p-phosphate at 7 days |  | Baseline and 7 days | 
| Change from baseline p-potassium at 7 days |  | Baseline and 7 days | 
| Change from baseline p-ALAT at 7 days |  | Baseline and 7 days | 
| Change from baseline p-alkaline phosphatase at 7 days |  | baseline and 7 days | 
| Change from baseline p-bilirubine at 7 days |  | baseline and 7 days | 
| Change from baseline INR at 7 days |  | baseline and 7 days | 
| Number of patients who died (mortality) |  | up to 3 months | 
| Number of patients with pneunomia |  | Up to one week | 
| Number of patients with gastrointestinal complications | Gastrointestinal complications monitored daily are: Nausea, Vomiting, Constipation, Diarrhea, Abdominal pain | Up to one week | 
| Change from baseline urine-ketones at 7 days |  | Baseline and 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, ketogenic diet, ketosis, ischemia, brain, ketones, hyperglycemia, neuroprotection