Energy Expenditure and Quality of Life in Epilepsy

Epilepsy Clinical Trial

Official title:

Effects of Ketogenic Diet on Epilepsy: Metabolism and Quality of Life

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04546711
• Other study ID #: 2020-0371
• Secondary ID: A535100SMPH/NEUR
• Status: Withdrawn
• Start date: June 2023
• Est. completion date: August 2025

Study information

• Verified date: June 2023
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main objectives of this study are to investigate the influence of the ketogenic diet (KD), standard care for patients assisted in the UW Health Adult Epilepsy Dietary Therapy Clinic, on changes in the frequency and severity of seizures, QoL, energy substrate metabolism, body energy expenditure components, fat mass and fat-free mass in adults with epilepsy. To achieve this objective, twenty-five male and female participants between the ages of 18 and 45 years (or over 18 years for remote participation), who accepted to initiate the KD as a standard of care prescribed by their physician, will be recruited according to inclusion/exclusion criteria. Participants will be on study for 6 months.

Description:

The ketogenic diet (KD) is a high fat, very low carbohydrate diet that promotes a variety of changes in the chemical processes on the body associated with reduced frequency and severity of seizures in patients with epilepsy. The reasons for this improvement are not yet fully understood and the answers can be related to changes in the biochemical process and the use of different substrates as the main source of energy for the body.

The quality of life (QoL) of patients with epilepsy is highly affected by stigmatization, difficulties with employment, and physical limitations. There is some evidence that the KD may have beneficial effects on QoL in patients with epilepsy, which can be investigated by changes in body energy expenditure (e.g. physical activity level). Studies that associate changes in body energy requirements, body composition and biochemical measures with seizures and QoL are currently limited in the scientific literature.

The main objectives of this study are to investigate the influence of the KD on changes in the frequency and severity of seizures, QoL, energy substrate metabolism, body energy expenditure components, fat mass and fat-free mass in adults with epilepsy. To achieve this objective, twenty-five male and female participants between the ages of 18 and 45 years (or over 18 years old for remote participation, no metabolic analysis will be complete on remote participants) will be recruited according to inclusion/exclusion criteria. Data will be collected at baseline (time of enrollment), and again at 3 and 6 months following diet start. Stable isotope compounds (doubly labeled water) will assess total daily energy expenditure (TDEE) and body composition (fat mass; fat-free mass). Indirect calorimetry will assess the resting energy expenditure (REE) and respiratory quotient for energy substrate oxidation. Biochemical blood exams (fasting glucose and insulin, and ketone bodies) and anthropometric data will provide data on the nutritional and metabolic status of the participant. Seizure frequency, severity, and QoL will be evaluated using validated self-report questionnaires. The physical activity level, obtained through the ratio between TDEE and REE and by wearing of a physical activity monitor, will be used as a predictor of QoL.

The hypothesis is that KD therapy promotes differences in energy metabolism and energy substrate oxidation, which will lead to better metabolic control of epilepsy, reduced frequency and severity of seizures, and also an improved patient QoL. This study is expected to help elucidate the metabolic changes associated with reduced seizure frequency and severity, and improvement of QoL in patients with epilepsy.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (in person participation):

• aged 18-45

• Diagnosis of epilepsy

• Experience an average of 2 or more seizures per month during the 3 months prior to study

• Plan to start oral ketogenic diet therapy (e.g. with the modified Atkins diet)

• Have low average or higher cognitive/intellectual function and are able to complete self-report questionnaires

Inclusion Criteria for Remote Participation:

• over 18 years of age (no age limit)

• Diagnosis of epilepsy

• Experience an average of 2 or more seizures per month during the 3 months prior to study

• Plan to start oral ketogenic diet therapy (e.g. with the modified Atkins diet)

• Have low average or higher cognitive/intellectual function and are able to complete self-report questionnaires

Exclusion Criteria:

• Participants who report being claustrophobic

• Presence of edema, conditions or persistent side effects of medication use (e.g. vomiting, diarrhea, excessive sweating, and burns) that could cause alterations in the body hydration and consequently, be a bias in energy metabolism variables

• Currently using medications that may cause metabolic and/or absorptive alterations (e.g. diuretics, amphetamines, lipase inhibitors, corticosteroids, etc.)

• Unstable metabolic condition (e.g. persistent sodium <130 or glucose <50)

• Liver, kidney, or pancreatic disease

• Hypercholesterolemia (cholesterol > 300mg/dL)

• Currently pregnant or planning on becoming pregnant

• Fatty acid oxidation disorder or pyruvate carboxylase deficiency

• Already on ketogenic therapy

Related Conditions & MeSH terms

• Epilepsy

Intervention

Other:
• Ketogenic Diet
The ketogenic diet (KD) is a high fat, very low carbohydrate diet

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Frequency of Seizures Assessed with Participant Seizure Frequency Report	The hypothesis is that participants will have a significant reduction in seizures (>50%) at 3 and 6 months following the start of KD therapy.	baseline, 3 months, 6 months
Primary	Change in Severity of Seizures Assessed by Seizure Severity Questionnaire (SSQ)	The SSQ scores range from 1-7 with lower scores indicating improved status. The hypothesize is that participants will have a significant reduction in seizures (>50%) at 3 and 6 months following the start of KD therapy, which will also lead a significant reduction (p<0.05) of SSQ overall score.	baseline, 3 months, 6 months
Primary	Change in the Quality of Life in Epilepsy (QOLIE-31-P) Score	The QOLIE-31-P instruments include seven multi-item scales that tap the following health concepts: emotional well-being, social functioning, energy/fatigue, cognitive functioning, seizure worry, medication effects, and overall quality of life. The total range of possible scores is 0-100, higher scores indicate better well being. The hypothesis is that participants will have a significant reduction in seizures (>50%) at 3 and 6 months following the start of KD therapy, which will also lead to significant improvement (p<0.05) in the QoL overall score.	baseline, 3 months, 6 months
Secondary	Enhanced Metabolic Control of Epilepsy Assessed by Indirect Calorimetry	The hypothesis is that KD therapy will promote significant differences (compared to pre-diet baseline) in substrate oxidation (an increase in fat oxidation and a decrease in carbohydrate oxidation) which will correlate with seizure reduction.	baseline, 3 months, 6 months
Secondary	Change in Physical Activity Level (PAL) as Recorded by Actigraph Measurement	The hypothesis is that KD therapy will contribute to an increase of PAL (direct contribution of KD), leading to an increase of total daily energy expenditure (TDEE) (indirect contribution of KD).	baseline, 3 months, 6 months
Secondary	Change in Body Fat Mass	The hypothesis is that KD therapy will contribute to a decrease in fat mass, a maintenance of fat-free mass.	baseline, 3 months, 6 months