Efficacy and Safety of Ketogenic Diet as Adjunctive Treatment in Adults With Refractory Epilepsy

NCT01906398 | Unknown Phase 2

• 1 other identifier: maes 001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to obtain pilot data on safety and efficacy of ketogenic diet (KD) as adjunctive treatment of adults with refractory epilepsy. This will be an open label study comparing seizure frequency during 4 months of prospective baseline observation period with seizure frequency during 4 months of add-on KD treatment. 18-65 year old men and women with refractory epilepsy, defined as seizures persisting in spite of past/present treatments with ≥ 3 AEDs, with seizure frequency of ≥ 0.5/month, will be evaluated. Subjects with both primary generalized and localization-related epilepsy (PGE, LRE) will be recruited. Subjects will have had epilepsy for at least 2 years prior to enrollment. Following initial screening, subjects will be observed for 4 months, with no change in AEDs except when deemed necessary by the patient's neurologist according to standard clinical care. Patients will then start ketogenic diet. Evaluations will include seizure frequency using a seizure diary, adverse events, treatment compliance using urine and plasma ketone levels. Quality of life will be evaluated with a standardized questionnaire of Quality Of Life In patients with Epilepsy, QOLIE-31-P. Level of alertness will be evaluated with Epworth Sleepiness Scale. These questionnaires will be administered at each visit.

Conditions

Epilepsy

Keywords

Refractory epilepsy; ketogenic diet; efficacy

Outcome Measures

Primary Outcomes (1)

• Change from baseline in epileptic seizure frequency.

  Seizure frequency, adverse events and treatment compliance will be reviewed. The diet will be reviewed with the subject by the nutritionist before treatment initiation. Seizure frequency will be counted using a daily seizure diary. Subject's neurological and other clinical progress since the last visit will be reviewed. Concurrent medications will be documented. Vital signs and weight will be obtained, and a complete physical and neurological examination will be performed. Body mass index will be calculated. Subjects seizure/urine ketone diary will be reviewed at each visit. Treatment compliance will be evaluated with urine ketone levels using the diaries and with serum b-hydroxy-butyrate (b-OH-butyrate, BOH) levels.

  baseline, 8 months

Secondary Outcomes (1)

• Evaluate the number of participants with adverse events.

  baseline, 8 months

Other Outcomes (2)

• Changes from baseline in Quality of life.

  baseline, 8 months

• Changes from baseline in alertness.

  baseline, 8 months

Study Arms (1)

Experimental: ketogenic diet

OTHER

Treatment will consist of KD will consist of 3:1 \[fat\]: \[protein + carbohydrate\] weight ratio, with 1600 kcal restriction for patients with body mass index (BMI) of ≥ 21. The diet will be initiated with a 24 hour fast to induce ketosis. The diet will be supplemented with vitamins, calcium and phosphorus supplements to meet the requirements of US Dietary Reference Intakes (DRI) standard. If seizure frequency does not improve after 3 months of KD treatment, \[fat\]: \[protein + carbohydrate\] weight ratio will be increased to 4:1

Other: ketogenic diet

Interventions

ketogenic diet OTHER

KD will consist of 3:1 \[fat\]: \[protein + carbohydrate\] weight ratio, with 1600 kcal restriction

Experimental: ketogenic diet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65
• Stable epilepsy, either primary generalized or localization-related with partial complex seizures including partial complex seizures with or without secondary generalization, partial simple seizures with a clear motor component with or without secondary generalization, and partial simple seizures with secondary generalization; primary generalized tonic clonic seizures; and absence seizures of \> 10 sec duration.
• Stable AED doses for at least 30 days
• Epilepsy duration for \> 1 year
• Past/current treatment with \> 3 AEDs. Vagal nerve stimulation treatment will be allowed and will not count as an AED. Vagal nerve stimulation setting must be stable for 3 months prior to enrollment
• Seizure frequency of \> 0.5/month

You may not qualify if:

• Exclusively myoclonic seizures or absence seizures of ≤ 10 sec duration; simple partial seizures without motor components or secondary generalization
• Non-epileptic seizures
• Progressive neurological disease including neoplasm, central nerve system degenerative disorders including Alzheimer's disease, other forms of dementia
• Any systemic illness or unstable medical condition that might pose additional risk, including: renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, other unstable metabolic or endocrine disturbances, and active systemic cancer
• Familial hyperlipidemia or uncontrolled hyperlipidemia
• Body Mass Index (BMI) \< 18
• Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
• Psychosis within six months of enrollment.
• Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
• Pregnancy
• Use of any CNS-active investigational drugs within 3 months of enrollment.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• Mid-Atlantic Epilepsy and Sleep Center, LLC: lead

Study Sites (1)

MidAtlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

MeSH Terms

Conditions

Epilepsy; Drug Resistant Epilepsy

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Pavel Klein, MD

  Mid-Atlantic Epilepsy and Sleep center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: July 24, 2013
• Study Start: January 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 23, 2018

Record last verified: 2018-02

Locations

US (1)