Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00836836 |
| Other study ID # |
ModAtkins |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
May 2009 |
| Est. completion date |
March 2011 |
Study information
| Verified date |
January 2019 |
| Source |
All India Institute of Medical Sciences, New Delhi |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
