Clinical trial NCT01906398: Efficacy and Safety of Ketogenic Diet as Adjunctive Treatment in Adults With Refractory Epilepsy
Official title: Evaluation of the Efficacy and Safety of Ketogenic Diet as Adjunctive Treatment in Adults With Refractory Epilepsy: a Pilot Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Epilepsy
Keywords: Refractory epilepsy
ketogenic diet
efficacy
Lead sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC
Sponsor class: OTHER
First posted: 2013-07-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The goal of the present open label study is to obtain pilot data to evaluate the efficacy and safety of KD in adults with intractable epilepsy. Investigators will evaluate the effect of KD on seizure frequency and on adverse events. Investigators will also evaluate serum levels of the ketone body, βhydroxybutyrate (BOH) and of glucose in order to determine whether changes in serum levels of these substances correlate with KD-associated changes in seizure frequency. The data from the present study will be used to design a large randomized study.

Laboratory evaluations will include complete blood count (CBC), serum electrolytes, including calcium, phosphate and magnesium, renal and liver functions, including total protein and albumin, uric acid, fasting serum lipid profile, glucose and b- hydroxybutyrate (BOH) levels, serum carnitine level, serum a.m. trough antiepilepsy drugs levels, and urine calcium and creatinine level. They will be obtained twice at baseline a month apart and monthly during KD treatment.

Primary outcome measures will include average monthly seizure frequency and adverse events. Secondary outcome measures will include treatment compliance, quality of life questionnaire (QOLIE-31-P) scores, and Epworth Sleepiness Scale scores.

Eligibility criteria: Inclusion Criteria:

1. Age 18-65
2. 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.
3. Stable AED doses for at least 30 days
4. Epilepsy duration for \> 1 year
5. 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
6. Seizure frequency of \> 0.5/month

Exclusion Criteria:

1. Exclusively myoclonic seizures or absence seizures of ≤ 10 sec duration; simple partial seizures without motor components or secondary generalization
2. Non-epileptic seizures
3. Progressive neurological disease including neoplasm, central nerve system degenerative disorders including Alzheimer's disease, other forms of dementia
4. 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
5. Familial hyperlipidemia or uncontrolled hyperlipidemia
6. Body Mass Index (BMI) \< 18
7. Change in the dose of any Antiepileptic Drug within 30 days prior to enrollment
8. Psychosis within six months of enrollment.
9. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements;
10. Pregnancy
11. Use of any CNS-active investigational drugs within 3 months of enrollment.
12. Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Primary outcomes:
measure: Change from baseline in epileptic seizure frequency.
timeFrame: baseline, 8 months
Secondary outcomes:
measure: Evaluate the number of participants with adverse events.
timeFrame: baseline, 8 months
Other outcomes:
measure: Changes from baseline in Quality of life.
timeFrame: baseline, 8 months
measure: Changes from baseline in alertness.
timeFrame: baseline, 8 months
Locations:
city: Bethesda
country: United States
facility: MidAtlantic Epilepsy and Sleep Center
state: Maryland
Study officials:
affiliation: Mid-Atlantic Epilepsy and Sleep center
name: Pavel Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: