IF-MCT 16:8: Investigating the Influence of Intermittent Fasting With and Without MCTs in Patients With Drug-resistant Epilepsy (IF-MCT16:8)

• ClinicalTrials.gov Identifier: NCT06013761
• Recruitment Status: Recruiting
• First Posted: August 28, 2023
• Last Update Posted: August 28, 2023
• Sponsor: University Hospital Marburg
• Information provided by (Responsible Party): Susanne Knake, Philipps University Marburg Medical Center

Study Description

Brief Summary:

The objective of the prospective monocentric pilot trial is to investigate the influence of intermittent fasting with or without a once-daily intake with medium chain triglycerides (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a within-subject-crossover-design in 28 patients with drug-resistant epilepsy.

Condition or disease	Intervention/treatment	Phase
Epilepsy; Intermittent Fasting	Other: IF 16:8 as active comparator vs. IF MCT 16:8 as experimental arm	Not Applicable

Detailed Description:

One in three patients suffering epilepsy does not become seizure-free with conventional pharmacotherapy. The chance of seizure freedom with each additional medication is only in the single-digit percentage range. For this reason, additive therapies such as the ketogenic diet play an important role. By means of a ketogenic diet, a significant reduction in the frequency of seizures has been shown in various studies for children. The main goal is the body's own production of ketone bodies in the liver, which are used instead of glucose to produce the energy carrier ATP. This metabolic change results in biochemical, metabolic and hormonal changes that may reduce the severity and frequency of epileptic seizures, although the exact mechanisms are not yet understood. Common to all forms of ketogenic diets (e.g. classic kKD, modified Atkins diet, low glycemic index diet) is a specific preparation of each meal with plans for meals and often an initiation of additive therapy in the inpatient setting or by trained staff. Especially in adulthood, the lack of treatment adherence seems to play an important role in the effectiveness of the ketogenic diet. A form of ketogenic diet which might be more suitable for everyday use is intermittent fasting.

The primary aim of the prospective monocentric pilot trial is to investigate the effect of intermittent fasting with and without a once-daily intake of medium-chain triglycerides (MCTs) on the frequency of seizures in patients with therapy-refractory epilepsy. The effects of 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared to 12 weeks intermittent fasting with additional intake of exogenous medium chain triglycerides (IF MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy. Secondarily, the influence of this diet on the composition of the gut microbiome, the T-cell mediated innate immune system and neuronal signalling pathways and networks will be investigated.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Monocentric Randomized Experimental Pilot Trial Investigating the Influence of Intermittent Fasting According to the 16:8 Method With and Without Medium-chain Triglycerides (MCTs) on Seizure Frequency, Biomarkers and Neural Networks in Patients With Drug-resistant Epilepsy
• Actual Study Start Date: July 25, 2023
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: IF 16:8; 12 weeks intermittent fasting according to the 16:8 method (IF 16:8)	Other: IF 16:8 as active comparator vs. IF MCT 16:8 as experimental arm; 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared with 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy. In order to enable the highest possible adherence, there are no restrictions on the composition of the food.
Experimental: IF MCT 16:8; 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8)	Other: IF 16:8 as active comparator vs. IF MCT 16:8 as experimental arm; 12 weeks intermittent fasting according to the 16:8 method (IF 16:8) are compared with 12 weeks intermittent fasting with additional intake of exogenous MCTs (IF MCT 16:8) in a within-subject-crossover design in 28 patients with drug-resistant epilepsy. In order to enable the highest possible adherence, there are no restrictions on the composition of the food.

Outcome Measures

Primary Outcome Measures :

1. Effect of intermittent fasting according to the 16:8 method with and without exogenous MCTs on seizure frequency in drug-resistant epilepsy [ Time Frame: 3 months ]
   Monthly seizure frequency is recorded using standardized seizure diaries.

Secondary Outcome Measures :

1. Effect of intermittent fasting according to the 16:8 method on therapy adherence in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   The nutritional behavior during the studio is recorded using a standardized daily nutrition diary.
2. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on ketosis in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   All participants measure their ketosis weekly with a standardized ketosis device during the fasting episode and document this in a ketosis table provided.
3. Effect of intermittent fasting according to the 16:8 method on self-efficacy in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   Self-efficacy is determined using the scale of general self-efficacy expectation (Jerusalem & Schwarzer). This includes 10 items with 4 degrees. High scores mean a high level of general self-efficacy expectation.
4. Effect of intermittent fasting according to the 16:8 method on life-quality in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   Life-quality is measured using the standardized questionnaire on life quality.
5. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on biomarkers in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   The metabolome is examined using a mass spectroscopic blood sample. The microbiome is examined using a standardized stool sample using next-generation sequencing.
6. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neural networks in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   Neural networks are measured using magnetic resonance imaging (diffusion tensor imaging and resting state MRI).
7. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on immune status in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   The immune status and in particular the T-cell mediated innate immune response is determined serologically.
8. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on fatigue in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   Fatigue is measured using the standardized Fatigue-Impact-Scale (FIS)-Test.
9. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on attention in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
   Attention is measured using the standardized test battery for attention testing (TAP-Test).
10. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on neurotransmitter gamma-aminobutyric acid (GABA)in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
    The change in the neurotransmitter GABA is examined serologically over the period of the study phase.
11. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on stress response in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
    Stress response in hair cortisol of all participants is recorded using several hair samples.
12. Effect of intermittent fasting according to the 16:8 method with exogenous MCTs on intima media thickness in patients with drug-resistant epilepsy [ Time Frame: 3 months ]
    Intima media thickness of all participants will be recorded with a duplex sonographic examination of the arteries supplying the brain.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects able to provide informed consent
• Drug-resistant epilepsy
• At least 3 seizures per month

Exclusion Criteria:

• Pregnancy
• Breast feeding period
• Metabolic disorder (e.g. diabetes, liver cirrhosis, kidney disease)
• Eating Disorder (e.g. anorexia, bulimia)
• Chronic inflammatory gut disease
• Active cancerous disease
• Antibiotics within the last 3 months

Contacts and Locations

Contacts

Contact: Wiebke Hahn, MD; +49 642158 65348; Hahnwi@staff.uni-marburg.de

Locations

Germany

Philipps University Marburg, Faculty of Medicine, Department of Neurology, Epilepsy Center; Recruiting

Marburg, Hessen, Germany, Baldingerstr., 35043

Contact: Department of Neurology, Epilepsy Center +49 6421 5865348 ezm@med.uni-marburg.de

Sponsors and Collaborators

University Hospital Marburg

Investigators

• Principal Investigator: Wiebke Hahn, MD; Philipps University Marburg Medical Center

More Information

• Responsible Party: Susanne Knake, Principal investigator, Philipps University Marburg Medical Center
• ClinicalTrials.gov Identifier: NCT06013761
• Other Study ID Numbers: 23-92 BO
• First Posted: August 28, 2023
• Last Update Posted: August 28, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Susanne Knake, Philipps University Marburg Medical Center:

Drug-resistant epilepsy; Intermittent fasting; Seizure frequency; Biomarkers; Neural networks; Microbiome

Additional relevant MeSH terms:

Epilepsy; Drug Resistant Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases