Epileptic SpasmsPhase 2/3NCT03807141
Evaluation of the Modified Atkins Diet in Children With Epileptic Spasms
A Phase 2/3 study testing Modified Atkins diet in people with Epileptic Spasms, run by Lady Hardinge Medical College at 1 site in India.
Trial summary
Epileptic spasms are a difficult to treat epileptic condition in young children. The first line treatment is hormonal treatment, in the form of ACTH or oral steroids, which are effective in 60-70% of children. Read more about this study
- Who is it for?
- Ages 9 months to 3 years
- Conditions the study is for
- Epileptic Spasms
- What is being tested?
- Modified Atkins diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteIndia
- Study dates
- 15 Jan 2019to 31 Mar 2022
- Phase
- Phase 2/3
- 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 9 months to 3 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 9 months to 3 years
- Presence of epileptic spasms in clusters in child 9 months to <3years of age, with electroencephalographic evidence of hypsarrhythmia or its variants, persisting, at least one cluster per day, despite treatment with either oral corticosteroids or adrenocorticotrophic hormone (ACTH) and one additional anticonvulsant (valproate/ benzodiazepine/ vigabatrin/ topiramate/ zonisamide/ levetiracetam) for at least 4 weeks.
Who cannot join
- Children with known or suspected inborn error of metabolism
- Children with renal, pulmonary, cardiac or hepatic dysfunction
- Severe malnutrition (weight for length or weight for height less than -3 Z score as per WHO growth charts)
- Motivational or psychosocial issues in the family which might affect the compliance
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Lady Hardinge Medical College
New Delhi, National Capital Territory of Delhi, 110018
Suvasini Sharma, 9910234344, sharma.suvasini@gmail.com
About this study
Official title: Evaluation of the Modified Atkins Diet in Children With Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial
Epileptic spasms are a difficult to treat epileptic condition in young children. The first line treatment is hormonal treatment, in the form of ACTH or oral steroids, which are effective in 60-70% of children. The condition does not respond well to other anti-epileptic drugs except vigabatrin which is not approved and hence has limited availability and high cost in India. The ketogenic diet, a high fat low carbohydrate diet has been found to be effective in refractory childhood epilepsy especially epileptic spasms. However, the ketogenic diet restricts calories and proteins and required strict weighing of foods. The modified Atkins diet (MAD) is a less restrictive diet which is easier for the parents to prepare and for the children to consume. In this study, it is planned to evaluate the efficacy of the MAD in children with epileptic spasms refractory to hormonal treatment in a randomized controlled trial.
Read the detailed description
Epileptic spasms comprise an infantile epileptic encephalopathy characterized by hypsarrhythmia on EEG, and frequent neurodevelopmental regression. Unfortunately the treatment of this disorder remains difficult. The first-line options which include hormonal therapy, i.e., adrenocorticotropic hormone (ACTH) or oral corticosteroids, and vigabatrin are effective in 60-70% of the patients. Hormonal therapy is considered the best available treatment. Vigabatrin being expensive and of limited availability is not a feasible option for most patients in our setting. Also, these are associated with significant side effects, and high relapse rates. Newer drugs such as topiramate, zonisamide, and levetiracetam have also been evaluated; however these drugs are less effective than ACTH. The ketogenic diet (KD) is a high fat, low carbohydrate diet. It has been used for treatment of intractable childhood epilepsy. The KD has also been shown in three retrospective studies to be effective for intractable infantile spasms; often after ACTH and vigabatrin have failed. A few previous studies have shown good efficacy of the ketogenic diet on infantile spasms. The traditional ketogenic diet, with 4:1 ratio of fat: carbohydrate + protein has its drawbacks. It restricts calories and fluids, and requires weighing of foods. Protein is generally restricted to 1 g/kg/day, with the majority of remaining calories in the form of fat. This may lead to hypoproteinemia and growth problems. Hospitalization is generally advocated for diet initiation, both for fasting and non-fasting initiation. Side effects of the diet include kidney stones, constipation, acidosis, diminished growth, weight loss, and hyperlipidemia.
The modified Atkins diet is a non-pharmacologic therapy for intractable childhood epilepsy that was designed to be a less restrictive alternative to the traditional ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Early studies have demonstrated efficacy and safety. Preliminary data have shown efficacy in refractory infantile spasms. Modified Atkins diet may be of special importance in infants, as proteins are not restricted; hence fewer problems with growth are expected. This diet is also ideal for resource-constraint settings with paucity of trained dieticians. Hence this study has been planned to evaluate the efficacy and tolerability of the modified Atkins diet in children with epileptic spasms refractory to hormonal treatment in a randomized controlled trial.
- Conditions
- Epileptic Spasms
- Being tested
- Modified Atkins diet
- Medical subject headings
- Spasms, Infantile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Atkins dietOther
This is a modified version of the ketogenic diet where-in carbohydrates are restricted without any protein or calorie restriction.
| Study group | Role | What they receive |
|---|---|---|
| Diet arm | Experimental | Modified Atkins diet will be administered with carbohydrate restriction to 10 grams per day. Proteins will be allowed unrestricted and fats will be actively encouraged.
The ongoing antiepileptic medication will be continued unchanged Receives: Other: Modified Atkins diet |
| Control | No intervention | The control group will continue their anti-epileptic medication unchanged with no additional dietary input |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of children who achieved spasm freedom as per parental reports at 4 weeks, in both the groups
The proportion of children who achieve spasm freedom for at least 48 hours as per parental reports at the end of 4 weeks will be evaluated in the both the groups
Measured: 4 weeks
Secondary outcomes (3)
Proportion of children who achieved >50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.
Proportion of children who achieved >50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.
Measured: 4 weeks
Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.
Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.
Measured: 4 weeks
Description and proportion of the adverse effects of the diet as per parental reports in the diet group
Description and proportion of the adverse effects of the diet as per parental reports in the diet group
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2019
- Study start15 Jan 2019
- Primary completion14 Jan 2022 (estimated)
- Study completion31 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Epileptic SpasmsStudies 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized controlled trial
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lady Hardinge Medical College
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Suvasini Sharma, Lady Hardinge Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03807141
- Sponsor's protocol ID
- MADISRCT
- Status last verified
- Feb 2019
- First submitted
- 4 Jan 2019
- Last updated
- 5 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sharma S, Goel S, Kapoor D, Garg D, Panda I, Elwadhi A, Patra B, Mukherjee SB, Pemde H. Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial. J Child Neurol. 2021 Jul;36(8):686-691. doi: 10.1177/08830738211004747. Epub 2021 Apr 9.
PubMed 33834913
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Modified Atkins Diet in Children With Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03807141
- Acronym / sponsor ID
- MADISRCT
- Conditions
- Epileptic Spasms
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Lady Hardinge Medical CollegeOther government
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 14 Jan 2022 (estimated)
- Study completion
- 31 Mar 2022 (estimated)
- First posted
- 16 Jan 2019 (actual)
- 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.
Epileptic spasms are a difficult to treat epileptic condition in young children. The first line treatment is hormonal treatment, in the form of ACTH or oral steroids, which are effective in 60-70% of children. The condition does not respond well to other anti-epileptic drugs except vigabatrin which is not approved and hence has limited availability and high cost in India. The ketogenic diet, a high fat low carbohydrate diet has been found to be effective in refractory childhood epilepsy especially epileptic spasms. However, the ketogenic diet restricts calories and proteins and required strict weighing of foods. The modified Atkins diet (MAD) is a less restrictive diet which is easier for the parents to prepare and for the children to consume. In this study, it is planned to evaluate the efficacy of the MAD in children with epileptic spasms refractory to hormonal treatment in a randomized controlled trial.
Detailed description
Epileptic spasms comprise an infantile epileptic encephalopathy characterized by hypsarrhythmia on EEG, and frequent neurodevelopmental regression. Unfortunately the treatment of this disorder remains difficult. The first-line options which include hormonal therapy, i.e., adrenocorticotropic hormone (ACTH) or oral corticosteroids, and vigabatrin are effective in 60-70% of the patients. Hormonal therapy is considered the best available treatment. Vigabatrin being expensive and of limited availability is not a feasible option for most patients in our setting. Also, these are associated with significant side effects, and high relapse rates. Newer drugs such as topiramate, zonisamide, and levetiracetam have also been evaluated; however these drugs are less effective than ACTH. The ketogenic diet (KD) is a high fat, low carbohydrate diet. It has been used for treatment of intractable childhood epilepsy. The KD has also been shown in three retrospective studies to be effective for intractable infantile spasms; often after ACTH and vigabatrin have failed. A few previous studies have shown good efficacy of the ketogenic diet on infantile spasms. The traditional ketogenic diet, with 4:1 ratio of fat: carbohydrate + protein has its drawbacks. It restricts calories and fluids, and requires weighing of foods. Protein is generally restricted to 1 g/kg/day, with the majority of remaining calories in the form of fat. This may lead to hypoproteinemia and growth problems. Hospitalization is generally advocated for diet initiation, both for fasting and non-fasting initiation. Side effects of the diet include kidney stones, constipation, acidosis, diminished growth, weight loss, and hyperlipidemia.
The modified Atkins diet is a non-pharmacologic therapy for intractable childhood epilepsy that was designed to be a less restrictive alternative to the traditional ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Early studies have demonstrated efficacy and safety. Preliminary data have shown efficacy in refractory infantile spasms. Modified Atkins diet may be of special importance in infants, as proteins are not restricted; hence fewer problems with growth are expected. This diet is also ideal for resource-constraint settings with paucity of trained dieticians. Hence this study has been planned to evaluate the efficacy and tolerability of the modified Atkins diet in children with epileptic spasms refractory to hormonal treatment in a randomized controlled trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Diet arm | Experimental | Other: Modified Atkins dietModified Atkins diet will be administered with carbohydrate restriction to 10 grams per day. Proteins will be allowed unrestricted and fats will be actively encouraged. The ongoing antiepileptic medication will be continued unchanged |
| Control | No intervention | –The control group will continue their anti-epileptic medication unchanged with no additional dietary input |
Who may qualify
- Ages
- 9 months to 3 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Age 9 months to 3 years
- Presence of epileptic spasms in clusters in child 9 months to <3years of age, with electroencephalographic evidence of hypsarrhythmia or its variants, persisting, at least one cluster per day, despite treatment with either oral corticosteroids or adrenocorticotrophic hormone (ACTH) and one additional anticonvulsant (valproate/ benzodiazepine/ vigabatrin/ topiramate/ zonisamide/ levetiracetam) for at least 4 weeks.
Key exclusion criteria (4 listed)
- Children with known or suspected inborn error of metabolism
- Children with renal, pulmonary, cardiac or hepatic dysfunction
- Severe malnutrition (weight for length or weight for height less than -3 Z score as per WHO growth charts)
- Motivational or psychosocial issues in the family which might affect the compliance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Atkins dietThis is a modified version of the ketogenic diet where-in carbohydrates are restricted without any protein or calorie restriction. | Other | Diet arm |
Primary outcome
Proportion of children who achieved spasm freedom as per parental reports at 4 weeks, in both the groups
Time frame: 4 weeks
The proportion of children who achieve spasm freedom for at least 48 hours as per parental reports at the end of 4 weeks will be evaluated in the both the groups
3 secondary outcomes
Proportion of children who achieved >50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.
Time frame: 4 weeks
Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.
Time frame: 4 weeks
Description and proportion of the adverse effects of the diet as per parental reports in the diet group
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
- Derived from this study: PubMed 33834913Sharma S, Goel S, Kapoor D, Garg D, Panda I, Elwadhi A, Patra B, Mukherjee SB, Pemde H. Evaluation of the Modified Atkins Diet for the Treatment of Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial. J Child Neurol. 2021 Jul;36(8):686-691. doi: 10.1177/08830738211004747. Epub 2021 Apr 9.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Modified Atkins diet in people with Epileptic Spasms, run by Lady Hardinge Medical College at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Feb 2019. 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 India. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Suvasini Sharma (09910234344, sharma.suvasini@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of children who achieved spasm freedom as per parental reports at 4 weeks, in both the groups (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03807141, which also lists 1 linked publication.
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 5 Feb 2019.