Lafora DiseaseNCT00007124
Ketogenic Diet in Lafora Disease
An observational study of Lafora Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Lafora Disease
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Nov 2002
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Males and females older than 10 years will be eligible for this study. Younger children may not be sufficiently cooperative.
Women of child-bearing age must be using adequate contraceptive method for at least one month prior to and during participation in the study.
All will carry the diagnosis of Lafora disease based on the presence of characteristic clinical history and neurological findings.
All will have a relatively advanced disease with at least one of the three cardinal neurological manifestations: myoclonus, epilepsy and cognitive decline.
All patients will have histological or (preferable) genetic confirmation of diagnosis.
All patients will also be on stable doses of concomitant medications for at least 2 weeks prior to the onset of the study.
Patients must not have the presence or history of any medical condition that can reasonably be expected to subject the patient to unwarranted risk.
Patients must have no clinically significant laboratory abnormality that can reasonably be expected to subject the patient to unwarranted risk.
Patients must not have contraindications to the use of ketogenic diet: carnitine deficiency, organic acidurias, defects in beta-oxidation, clinically significant nephrolithiasis, and those who are immunosuppressed .
Pregnant women will be excluded. Those not practicing effective means of birth control will be excluded since the influence of this investigational therapy on the unborn child and reproductive organs is unknown. Urine pregnancy test will be performed on women of childbearing age.
Forbidden medications:
No significant interactions are generally expected between therapy with ketogenic diet and other concomitant medications. However, those carbohydrate-containing drug preparations which may interfere with the achievement of persistent ketosis, will be avoided as possible. Moreover, in case of unexpected hospital visits requiring IV fluids, patients and their parents will be asked to advise the treating medical staff on the need to avoid the use of dextrose-containing solutions, to minimize risks of iatrogenic seizures.
Anticonvulsant medications, in general, do not negatively interact with the ketogenic diet, but concomitant use of drugs such as Topiramate (sometimes associated with nephrolithiasis) will be avoided as possible.
As mentioned earlier, doses of VPA, commonly used in patients with myoclonic epilepsy, will be decreased by 25%, as KD may significantly elevate serum plasma levels of VPA.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: A Trial of Ketogenic Diet in Lafora Disease
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:
Read more
- 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.
Read the detailed 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.
- Conditions
- Lafora Disease
- Keywords
- Myoclonus, Epilepsy, Dementia, Polyglucosan, Insulin, Lafora Disease, Restrictive Carbohydrate Diet
- Medical subject headings
- Lafora Disease, Myoclonus, Epilepsy, Dementia, Insulin Resistance
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2000 (estimated)
- Study startDec 2000
- Study completionNov 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lafora DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 15 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007124
- Sponsor's protocol ID
- 010042
- Other IDs
- 01-N-0042
- Status last verified
- Nov 2002
- First submitted
- 7 Dec 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Elliott EJ, Talbot IC, Pye IF, Hodges S, Swift PG, Tanner MS. Lafora disease: a progressive myoclonus epilepsy. J Paediatr Child Health. 1992 Dec;28(6):455-8. doi: 10.1111/j.1440-1754.1992.tb02717.x.
PubMed 1466943Berkovic SF, So NK, Andermann F. Progressive myoclonus epilepsies: clinical and neurophysiological diagnosis. J Clin Neurophysiol. 1991 Jul;8(3):261-74.
PubMed 1918332Federico A, D'Amore I, Palladini G, Medolago-Albani L, Guazzi GC, Tomaccini D. Lafora's disease. Clinical, histological ultrastructural and biochemical study. Acta Neurol (Napoli). 1980 Dec;2(6):466-75. No abstract available.
PubMed 6457518
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of Ketogenic Diet in Lafora Disease
- ClinicalTrials.gov ID
- NCT00007124
- Acronym / sponsor ID
- 010042
- Conditions
- Lafora Disease
- Keywords
- Myoclonus, Epilepsy, Dementia, Polyglucosan, Insulin, Lafora Disease, Restrictive Carbohydrate Diet
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Dec 2000
- Study completion
- Nov 2002
- First posted
- 8 Dec 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 1466943Elliott EJ, Talbot IC, Pye IF, Hodges S, Swift PG, Tanner MS. Lafora disease: a progressive myoclonus epilepsy. J Paediatr Child Health. 1992 Dec;28(6):455-8. doi: 10.1111/j.1440-1754.1992.tb02717.x.
- Background: PubMed 1918332Berkovic SF, So NK, Andermann F. Progressive myoclonus epilepsies: clinical and neurophysiological diagnosis. J Clin Neurophysiol. 1991 Jul;8(3):261-74.
- Background: PubMed 6457518Federico A, D'Amore I, Palladini G, Medolago-Albani L, Guazzi GC, Tomaccini D. Lafora's disease. Clinical, histological ultrastructural and biochemical study. Acta Neurol (Napoli). 1980 Dec;2(6):466-75. No abstract available.
Related trials for Lafora Disease
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lafora Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00007124, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.