<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03807141</url>
  </required_header>
  <id_info>
    <org_study_id>MADISRCT</org_study_id>
    <nct_id>NCT03807141</nct_id>
  </id_info>
  <brief_title>Evaluation of the Modified Atkins Diet in Children With Epileptic Spasms</brief_title>
  <official_title>Evaluation of the Modified Atkins Diet in Children With Epileptic Spasms Refractory to Hormonal Therapy: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lady Hardinge Medical College</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lady Hardinge Medical College</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Epileptic spasms are a difficult to treat epileptic condition in young children. The first&#xD;
      line treatment is hormonal treatment, in the form of ACTH or oral steroids, which are&#xD;
      effective in 60-70% of children. The condition does not respond well to other anti-epileptic&#xD;
      drugs except vigabatrin which is not approved and hence has limited availability and high&#xD;
      cost in India. The ketogenic diet, a high fat low carbohydrate diet has been found to be&#xD;
      effective in refractory childhood epilepsy especially epileptic spasms. However, the&#xD;
      ketogenic diet restricts calories and proteins and required strict weighing of foods. The&#xD;
      modified Atkins diet (MAD) is a less restrictive diet which is easier for the parents to&#xD;
      prepare and for the children to consume. In this study, it is planned to evaluate the&#xD;
      efficacy of the MAD in children with epileptic spasms refractory to hormonal treatment in a&#xD;
      randomized controlled trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Epileptic spasms comprise an infantile epileptic encephalopathy characterized by&#xD;
      hypsarrhythmia on EEG, and frequent neurodevelopmental regression. Unfortunately the&#xD;
      treatment of this disorder remains difficult. The first-line options which include hormonal&#xD;
      therapy, i.e., adrenocorticotropic hormone (ACTH) or oral corticosteroids, and vigabatrin are&#xD;
      effective in 60-70% of the patients. Hormonal therapy is considered the best available&#xD;
      treatment. Vigabatrin being expensive and of limited availability is not a feasible option&#xD;
      for most patients in our setting. Also, these are associated with significant side effects,&#xD;
      and high relapse rates. Newer drugs such as topiramate, zonisamide, and levetiracetam have&#xD;
      also been evaluated; however these drugs are less effective than ACTH. The ketogenic diet&#xD;
      (KD) is a high fat, low carbohydrate diet. It has been used for treatment of intractable&#xD;
      childhood epilepsy. The KD has also been shown in three retrospective studies to be effective&#xD;
      for intractable infantile spasms; often after ACTH and vigabatrin have failed. A few previous&#xD;
      studies have shown good efficacy of the ketogenic diet on infantile spasms. The traditional&#xD;
      ketogenic diet, with 4:1 ratio of fat: carbohydrate + protein has its drawbacks. It restricts&#xD;
      calories and fluids, and requires weighing of foods. Protein is generally restricted to 1&#xD;
      g/kg/day, with the majority of remaining calories in the form of fat. This may lead to&#xD;
      hypoproteinemia and growth problems. Hospitalization is generally advocated for diet&#xD;
      initiation, both for fasting and non-fasting initiation. Side effects of the diet include&#xD;
      kidney stones, constipation, acidosis, diminished growth, weight loss, and hyperlipidemia.&#xD;
&#xD;
      The modified Atkins diet is a non-pharmacologic therapy for intractable childhood epilepsy&#xD;
      that was designed to be a less restrictive alternative to the traditional ketogenic diet.&#xD;
      This diet is started on an outpatient basis without a fast, allows unlimited protein and fat,&#xD;
      and does not restrict calories or fluids. Early studies have demonstrated efficacy and&#xD;
      safety. Preliminary data have shown efficacy in refractory infantile spasms. Modified Atkins&#xD;
      diet may be of special importance in infants, as proteins are not restricted; hence fewer&#xD;
      problems with growth are expected. This diet is also ideal for resource-constraint settings&#xD;
      with paucity of trained dieticians. Hence this study has been planned to evaluate the&#xD;
      efficacy and tolerability of the modified Atkins diet in children with epileptic spasms&#xD;
      refractory to hormonal treatment in a randomized controlled trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 14, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of children who achieved spasm freedom as per parental reports at 4 weeks, in both the groups</measure>
    <time_frame>4 weeks</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of children who achieved &gt;50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Proportion of children who achieved &gt;50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Description and proportion of the adverse effects of the diet as per parental reports in the diet group</measure>
    <time_frame>4 weeks</time_frame>
    <description>Description and proportion of the adverse effects of the diet as per parental reports in the diet group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Epileptic Spasms</condition>
  <arm_group>
    <arm_group_label>Diet arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.&#xD;
The ongoing antiepileptic medication will be continued unchanged</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group will continue their anti-epileptic medication unchanged with no additional dietary input</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Modified Atkins diet</intervention_name>
    <description>This is a modified version of the ketogenic diet where-in carbohydrates are restricted without any protein or calorie restriction.</description>
    <arm_group_label>Diet arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 9 months to 3 years&#xD;
&#xD;
          -  Presence of epileptic spasms in clusters in child 9 months to &lt;3years of age, with&#xD;
             electroencephalographic evidence of hypsarrhythmia or its variants, persisting, at&#xD;
             least one cluster per day, despite treatment with either oral corticosteroids or&#xD;
             adrenocorticotrophic hormone (ACTH) and one additional anticonvulsant (valproate/&#xD;
             benzodiazepine/ vigabatrin/ topiramate/ zonisamide/ levetiracetam) for at least 4&#xD;
             weeks.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with known or suspected inborn error of metabolism&#xD;
&#xD;
          -  Children with renal, pulmonary, cardiac or hepatic dysfunction&#xD;
&#xD;
          -  Severe malnutrition (weight for length or weight for height less than -3 Z score as&#xD;
             per WHO growth charts)&#xD;
&#xD;
          -  Motivational or psychosocial issues in the family which might affect the compliance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>9 Months</minimum_age>
    <maximum_age>3 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Suvasini Sharma</last_name>
    <phone>09910234344</phone>
    <email>sharma.suvasini@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Lady Hardinge Medical College</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110018</zip>
        <country>India</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suvasini Sharma</last_name>
      <phone>9910234344</phone>
      <email>sharma.suvasini@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>February 1, 2019</last_update_submitted>
  <last_update_submitted_qc>February 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lady Hardinge Medical College</investigator_affiliation>
    <investigator_full_name>Suvasini Sharma</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsy</mesh_term>
    <mesh_term>Spasm</mesh_term>
    <mesh_term>Spasms, Infantile</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03807141
org study id: MADISRCT
nct id: NCT03807141
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of children who achieved spasm freedom as per parental reports at 4 weeks, in both the groups
time frame: 4 weeks
description: 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
measure: 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
description: Proportion of children who achieved >50% reduction of clinical spasm, as per parental reports at 4 weeks, in both the groups.
measure: Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.
time frame: 4 weeks
description: Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 4 weeks in both the groups.
measure: Description and proportion of the adverse effects of the diet as per parental reports in the diet group
time frame: 4 weeks
description: Description and proportion of the adverse effects of the diet as per parental reports in the diet group
arm group label: Diet arm
arm group type: Experimental
description: 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
arm group label: Control
arm group type: No Intervention
description: The control group will continue their anti-epileptic medication unchanged with no additional dietary input
intervention type: Other
intervention name: Modified Atkins diet
description: This is a modified version of the ketogenic diet where-in carbohydrates are restricted without any protein or calorie restriction.
arm group label: Diet arm
criteria: 
gender: All
minimum age: 9 Months
maximum age: 3 Years
healthy volunteers: No
last name: Suvasini Sharma
phone: 09910234344
email: sharma.suvasini@gmail.com
facility: 
status: Recruiting
contact: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Lady Hardinge Medical College
investigator full name: Suvasini Sharma
investigator title: Associate Professor
mesh term: Epilepsy
mesh term: Spasm
mesh term: Spasms, Infantile
sharing ipd: No