Modified Atkins Diet in Childhood Epilepsy
Condition: Refractory Childhood Epilepsy
MeSH terms: Epilepsy
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Seizures are a frequent cause of morbidity in the pediatric age group. Uncontrolled seizures
      pose a variety of risks to children, including higher rates of mortality, developmental delay
      and/or regression, and cognitive impairment. The ketogenic diet is a well known treatment
      option for refractory epilepsy. However it is very restrictive and requires strict weighing
      of foods. The modified Atkins diet is a dietary therapy for intractable childhood epilepsy
      that was designed to be a less restrictive alternative to the traditional ketogenic diet.
      Early studies have demonstrated efficacy and safety.There are no randomized trials evaluating
      the efficacy of the modified Atkins diet in children with refractory epilepsy. Hence this
      study has been planned to investigate whether there are clear benefits in terms of seizure
      control in children with refractory epilepsy who are treated with the modified Atkins diet,
      versus controls.
    

Detailed description: 
      Several severe catastrophic epilepsies present in childhood, including severe infantile
      myoclonic epilepsy, Lennox Gastaut syndrome and myoclonic-astatic epilepsy (Doose syndrome).
      Seizures in these disorders are difficult to control; sometimes only at the expense of
      multiple and toxic levels of antiepileptic medications.Epilepsy surgery is feasible only in a
      very small number, also the costs are prohibitively high.

      Uncontrolled seizures pose a variety of risks to children, including higher rates of
      mortality, developmental delay and/or regression, and cognitive impairment. Thus effective
      treatment to control seizures is fundamental to improving overall outcome in childhood
      epilepsy. The shortcomings of antiepileptic drug therapy and epilepsy surgery have made the
      need for alternative treatments.

      The ketogenic diet is one of the oldest available treatments for epilepsy. It is a medically
      supervised high fat, low carbohydrate, and restricted protein diet that maintains a chronic
      state of ketosis while providing proteins and calories for adequate growth. The ketogenic
      diet compares favourably with the newer antiepileptic drugs (AED's) which have been developed
      for the treatment epilepsy in children Studies on the newer antiepileptic drugs such as
      vigabatrin, lamotrigine, tiagabine and gabapentin indicate that only 3% to 10% of all
      intractable patients achieve complete relief of seizures with the introduction of these newer
      drugs. Whereas with the ketogenic diet, 33% of patients with intractable epilepsy have more
      than 50% reduction in seizures and 15-20% become seizure free.Also, many of the children who
      are maintained on the diet are able to have their antiepileptic drugs decreased or withdrawn.
      This leads to improvement in alertness, behaviour and cognition.

      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 nonpharmacologic 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.13-20 However these studies have been uncontrolled, and have enrolled small numbers of
      patients. There are no randomized control trials evaluating the efficacy of the modified
      Atkins diet in children and adults with refractory epilepsy. Hence this study has been was
      planned to investigate whether there are clear benefits in terms of seizure control in
      children with refractory epilepsy who are treated with the modified Atkins diet, versus
      controls.

      Eligible children will be randomized using computer generated random number tables in two
      groups: the intervention and the control arm. Both groups will undergo a baseline 4-week
      observation period, during which parents will be asked to maintain a daily seizure activity
      log; recording seizure type, duration and frequency. In the intervention arm, the children
      will start the modified Atkins diet after this 4-week baseline period. The control group will
      receive their normal diet with no dietetic input, and remain on the same on-going
      antiepileptic medication for the 3 months. Anti-epileptic medications will remain unchanged
      during the 3 month trial period in both groups, unless the change in AED regimen is medically
      indicated; e.g. drug side effects or status epilepticus; in which case standard therapy will
      be provided.

      Children will be reviewed as outpatients at 1, 2 and 3 months. Urinary ketones will be
      checked at each hospital visit. A 3-day dietary intake chart will be reviewed at each visit
      to compute calorie and carbohydrate intake, and reinforce compliance. Weight will be checked
      at each visit.

      Seizure frequencies will be recorded daily for the 4-week baseline period and the 3 month
      study period. At the end of the 3 month study period, the number of seizures in the preceding
      28 days will be used to calculate the mean seizure number, which will be expressed as a
      percentage of the mean baseline number of daily seizures (ie, the number of seizures during
      the 4 weeks before the child started either the diet or the control phase of the study).No
      changes will be made to the child's antiepileptic medication during the 4-week baseline or
      the 3-month study periods, unless medically indicated; e.g. drug side effects, or status
      epilepticus; in which case standard therapy will be provided.

      Tolerability of the diet and its side effects will be evaluated by means of parental
      interview at each visit: vomiting, lethargy, poor appetite, refusal to feed and constipation.
      Any other parental concerns or parental reports of side effects will also be noted.
    

Intervention name(s): Modified Atkins diet
Intervention type(s): Other
Intervention description(s): Modified Atkins Diet administration
Carbohydrates intake will be restricted to 10 grams/ day. (Carbohydrate values of various food items will be explained in detail, and exchange lists provided. Four 2.5 grams carbohydrate exchange items will be allowed in a day.)
Fats (e.g. cream, butter, oils, ghee) encouraged.
Proteins (cheese, fish, eggs, chicken, soya products) unrestricted.
Clear carbohydrate-fluids not restricted.
Calcium and multivitamin supplementation will be provided.
Other intervention name(s): Dietary intervention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Childhood epilepsy; ketogenic diet