Ketogenic Diet in Lafora Disease
Summary
This study will examine the effect of a restricted-carbohydrate diet (ketogenic diet) on Lafora disease-a severe neurological disease in which brain cells die because of abnormal accumulation of glucose (a type of sugar). Patients with Lafora disease have rapid neurological deterioration with myoclonus (brief muscle jerks), seizures and mental decline. At present there is no treatment to halt disease progression.
Patients 10 years of age and older with relatively advanced Lafora disease may be eligible for this study. Participants will be admitted to the Clinical Center for the first 4 weeks of this 6-month study for baseline testing and to start the ketogenic diet. They will have a complete medical history and physical examination, plus a detailed neurological examination and blood and urine tests. Procedures include:
- Magnetic resonance imaging (MRI) brain scans to provide information about brain chemistry
- Lumbar puncture (spinal tap) to analyze chemicals in cerebrospinal fluid
- Metabolic and endocrinological tests, including a glucose tolerance test, to evaluate the body's response to a large intake of oral glucose
- Standard neuropsychological tests
- Magnetic resonance spectroscopy of the brain and muscle
- Electroencephalography (EEG) to measure brain wave activity
- Electromyography (EMG) to measure muscle activity
- Evoked potentials (SEP and VEP) to study brain responses to mild electric or visual stimulation.
Transcranial magnetic stimulation (magnetic stimulation of the brain) may also be done to study the function of the brain cortex (outer nervous tissue of the brain) and the effects of treatment on brain excitability.
The ketogenic diet will begin after the tests are completed. The diet provides mainly fats to fuel the body, plus the recommended amount of protein and minimum carbohydrate. Vitamin and mineral supplements are provided to meet daily requirements. After 2 weeks on the diet, the patient will be discharged from the hospital and seen daily as an outpatient for another 1 to 2 weeks. During this time the patient or caregiver is trained in preparing the ketogenic diet, and then the patient is discharged to home. Throughout the study, disease symptoms will be assessed using standardized rating scales. Blood and urine tests will be done as needed, as will follow-up brain imaging, neuropsychological and neurophysiological evaluations.
A skin and/or muscle biopsy may be done at the first clinic visit to grow skin cells in culture and to analyze the skin and muscle under a microscope. The biopsy area is numbed with an anesthetic and a small piece of tissue is removed either with a needle, an instrument similar to a cookie-cutter or a knife. The skin cells may be used for metabolic studies and to obtain DNA for genetic testing.
At the end of the study, patients who responded well to the treatment with no significant adverse side effects may continue the diet for another 12 months. They will be followed at 3-month intervals to monitor side effects and treatment response.
Description
The objective of this study is to evaluate the acute effect and potential disease modifying effects of a restrictive minimum carbohydrate diet (ketogenic diet) in patients with Lafora Disease. Untreated Lafora Disease is rapidly progressive to death over about 10 years. In an open label, proof-of-principle clinical trial, the efficacy of the ketogenic diet will be assessed through the use of validated clinical scales, as well as surrogate neurophysiological and biochemical measures. Safety will be monitored by means of frequent clinical evaluations and laboratory tests.
Study Design
N/A
Conditions
Lafora Disease
Location
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda
Maryland
United States
20892
Status
Completed
Source
National Institutes of Health Clinical Center (CC)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00007124
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Lafora Disease
A form of stimulus sensitive myoclonic epilepsy inherited as an autosomal recessive condition. The most common presenting feature is a single seizure in the second decade of life. This is followed by progressive myoclonus, myoclonic seizures, tonic-clonic seizures, focal occipital seizures, intellectual decline, and severe motor and coordination impairments. Most affected individuals do not live past the age of 25 years. Concentric amyloid (Lafora) bodies are found in neurons, liver, skin, bone, and muscle (From Menkes, Textbook of Childhood Neurology, 5th ed, pp111-110)
Myoclonic Epilepsies, Progressive
A heterogeneous group of primarily familial disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.
Disease Reservoirs
Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (DISEASE VECTORS) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks.
Clinical Enzyme Tests
Analyses for a specific enzyme activity, or of the level of a specific enzyme that is used to assess health and disease risk, for early detection of disease or disease prediction, diagnosis, and change in disease status.
Disease Progression
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
Clinical Trials
None
PubMed Articles
Impaired autophagy in Lafora disease.
Lafora disease (LD) is a progressive, lethal, autosomal recessive, neurodegenerative disorder that manifests with myoclonus epilepsy. LD is characterized by the presence of intracellular inclusion bod...
Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism.
Lafora disease is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, intellectual, and progressive neurol...
Lafora disease (LD) is an autosomal recessive progressive myoclonic epilepsy characterized by the presence of intracellular polyglucosan inclusions commonly known as Lafora bodies in many tissues incl...
Lafora progressive myoclonus epilepsy, also known as Lafora disease (LD), is the most severe and fatal form of progressive myoclonus epilepsy with its typical onset during the late childhood or early...
A series of methyl maltotrioside phosphates were synthesized for application in the determination of the actual molecular substrate of the Lafora enzyme involved in Lafora disease. Several different s...
