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

Primary Purpose

Epilepsy

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

ketogenic diet

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Refractory epilepsy, ketogenic diet, efficacy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Sites / Locations

MidAtlantic Epilepsy and Sleep Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Experimental: ketogenic diet

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Evaluate the number of participants with adverse events.

Adverse events and treatment compliance will be reviewed.Subject's neurological and other clinical progress since the last visit will be reviewed.

Full Information

NCT ID

NCT01906398

First Posted

June 11, 2013

Last Updated

February 22, 2018

Sponsor

Mid-Atlantic Epilepsy and Sleep Center, LLC

1. Study Identification

Unique Protocol Identification Number

NCT01906398

Brief Title

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

Acronym

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

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Unknown status

Study Start Date

January 2013 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mid-Atlantic Epilepsy and Sleep Center, LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy

Keywords

Refractory epilepsy, ketogenic diet, efficacy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental: ketogenic diet

Arm Type

Other

Arm Description

Intervention Type

Other

Intervention Name(s)

ketogenic diet

Intervention Description

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

Primary Outcome Measure Information:

Title

Change from baseline in epileptic seizure frequency.

Description

Time Frame

baseline, 8 months

Secondary Outcome Measure Information:

Title

Evaluate the number of participants with adverse events.

Description

Adverse events and treatment compliance will be reviewed.Subject's neurological and other clinical progress since the last visit will be reviewed.

Time Frame

baseline, 8 months

Other Pre-specified Outcome Measures:

Title

Changes from baseline in Quality of life.

Description

Quality of life will be evaluated with a standardized questionnaire of quality of life in patients with epilepsy, QOLIE-31-P.

Time Frame

baseline, 8 months

Title

Changes from baseline in alertness.

Description

Alertness will be evaluated with Epworth Sleepiness Scale.

Time Frame

baseline, 8 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pavel Klein, MD

Organizational Affiliation

Mid-Atlantic Epilepsy and Sleep center

Official's Role

Principal Investigator

Facility Information:

Facility Name

MidAtlantic Epilepsy and Sleep Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20817

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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