Efficacy of Low Glycemic Index Diet Versus Modified Atkins Diet and Gluten Free Casein Free Diet as add-on Therapy With Standard of Care in Children With Autism Spectrum Disorder - A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 123
- 试验地点
- 1
- 主要终点
- To evaluate the efficacy of add-on LGIT vs MAD and GFCF diet along with standard of care in terms of mean reduction in CARS-2 score, at 6 months post intervention, in children with ASD aged 3-8 years.
研究概览
简要总结
Autism spectrum disorder (ASD) is a heterogenous, lifelong neurodevelopmental disorder with deficits in social communication and restrictive, repetitive patterns of behavior, with onset in the early developmental period leading to significant impairment in adaptive functioning. With the rising prevalence of ASD and expanding access to early intervention programs, there is a need for more efficacious therapies with a biological basis as additional interventions along with standard of care. The rationale for dietary therapies in autism being, the high rate of GI comorbidities and dysbiosis. Based on evidence from our centre, add-on modified Atkins diet and add-on gluten free, casein-free diet are superior to standard of care alone in improving core deficits (measured by CARS-2 score at 6 months ) in children with ASD. Low glycemic index diet is a comparitively less restricitive diet with better adverse effect profile, with preclinical evidence in ASD. It has been proven to be non inferior to MAD for drug refractory epilepsy, with no clinical trials in ASD. This clinical trial aims to learn if add-on low glycemic index diet works as well as modified Atkins diet and gluten free casein free diet along with standard of care in children aged 3 to 8 years with Autism Spectrum Disorder. The main question it aims to answer is:
In children aged 3 to 8 years with Autism Spectrum Disorder, what is the comparative efficacy of add-on low glycemic index diet versus Modified Atkins diet and Gluten free Casein free diet along with standard of care in reducing the CARS-2 score at 6 months post intervention?
Eligible children aged 3-8 years with ASD will be randomised into three arms:
- Low Glycemic Index diet arm: foods with glycemic index >50 would be excluded
- Modified Atkins diet arm: a high-fat, low carbohydrate diet in which carbohydrate intake would be restricted to 10 g/day
- Gluten-free casein-free diet arm: gluten (oats, barley, wheat, rye) and casein (milk and milk products) containing foods would be excluded
In all three arms, in addition to diet, standard of care involving behavioural therapy, speech therapy and occupational therapy would be continued.
Baseline investigations would be performed prior to diet initiation, and the diet introduced gradually over a period of 2 weeks. Participants would follow the diet for a period of 6 months, maintaining a dietary log. Weekly telephonic contacts and two monthly physical contacts would be made to ensure compliance and check for any adverse events.
Assessments will be performed at baseline, 3 months and 6 months post intervention in the form of autism severity, behavioral, neurocognitive and sleep assessment.
详细描述
Children aged 3 to 8 years presenting to pediatric neurology OPD and Autism clinic in the department of Pediatrics, AIIMS, New Delhi, will be screened for eligibility. Those children fulfilling the inclusion and exclusion criteria will be enrolled.
Eligible children will be randomised into three groups. Group I would receive add-on Low Glycemic Index diet (LGIT) with standard of care, Group II would receive add-on Modified Atkins diet (MAD) with standard of care and group III would receive add-on Gluten free casein free (GFCF) diet with standard of care. The process of randomisation will be done by a person who has no role in collecting the baseline variables, applying intervention, data collection or analysis of outcomes. Block randomisation would be performed in 1:1:1 ratio with variable block size using computer generated random numbers. These will be generated by a person not involved in the study.
Allocation concealment: Serially numbered, sealed, identical envelope containing the random allocation will be kept at study site as per allocation sequence.
Blinding : The study will be an open label randomised controlled trial. The individual performing behavioural and neuro-cognitive assessments will be blinded to the group to which the patient is randomised.
Baseline demographic details will be collected and following evaluation will be done at baseline, 3 months and 6 months post intervention:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 3 to 8 years diagnosed with ASD according to DSM -V criteria
排除标准
- •ASD in remission : DSM V criteria fulfilled only historically and/or current CARS-2 score <30
- •Genetic/acquired metabolic disorders including fatty acid oxidation defects, pyruvate carboxylase deficiency, porphyria, diabetes mellitus, dyslipidemia
- •Presence of kidney stones
- •Children with failure to thrive/underweight/stunting, poor oral intake
- •Gastroesophageal reflux
- •Chronic systemic illness: renal/cardiac/hepatic/lung disease, chronic metabolic acidosis, malabsorption
- •Changes in antipsychotic medications over the last 1 month
- •Associated epilepsy
- •Pre-existing food fads
- •Food allergies: to gluten and/or casein, celiac disease
- •Those who have been on Ketogenic diet/ Modified Atkins diet/ Low Glycemic Index Diet / Gluten free and/or Casein free diet in the last 6 months
- •Refusal of consent
研究组 & 干预措施
Low glycemic index diet with standard of care
Exclusion of high glycemic index foods (with Glycemic index >50), along with standard of care
干预措施: Low glycemic index diet with standard of care (Other)
Modified Atkins diet with standard of care
Modified Atkins diet: A less restrictive version of the ketogenic diet, with standard of care
干预措施: Modified Atkins diet with standard of care (Other)
Gluten free casein free diet with standard of care
Exclusion of gluten and casein containing foods, along with standard of care
干预措施: Gluten free casein free diet with standard of care (Other)
结局指标
主要结局
To evaluate the efficacy of add-on LGIT vs MAD and GFCF diet along with standard of care in terms of mean reduction in CARS-2 score, at 6 months post intervention, in children with ASD aged 3-8 years.
时间窗: Baseline and 6 months
Childhood Autism Rating Score (CARS-2) is a validated tool to assess the severity of ASD based on the core symptoms. It is a questionnaire including 15 items, each being scored on a scale from 1(no symptom) to 4 (severe symptom) at intervals of 0.5, which is completed by interviewing the primary caregiver as well as direct observation of the child. The standard version (CARS-ST) is for children less than 6 years or above 6 years with language impairment or with IQ\<80, while the high functioning version (CARS-HF) is for children older than 6 years who are verbally fluent with IQ\>80. The cutoffs for CARS-ST no autism/remission, mild-moderate and severe autsim respectively are 15-29.5, 30-36 and 37 - 60 respectively. Based on expert consensus from an expert elicitation procedure, a change of \>4.5 points is considered clinically relevant, to distinguish between interventions which are merely statistically significant from those which produce meaningful changes in behavioral outcome.
次要结局
- To evaluate the efficacy of add-on MAD vs GFCF diet in addition to standard of care in terms of mean reduction of CARS-2 score, at 6 months post intervention in children with ASD aged 3-8 years(Baseline and 6 months)
- To compare the change in the cognitive ability as measured by DQ (VABS) , SQ (VSMS) and IQ (MISIC) in children receiving add on LGIT vs MAD and GFCF along with standard of care in children with ASD aged 3-8 years at 3 months and 6 months post initiation(Baseline, 3 months and 6 months)
- To compare the quantitative reduction in symptoms of co-morbidities like inattention, hyperactivity, aggression (CBCL) and sleep related abnormalities (CHSQ-SF) in children with ASD in all three arms after follow up for 3 and 6 months.(Baseline, 3 months and 6 months)
- To assess the compliance in children aged 3-8 years with ASD receiving add-on LGIT, MAD and GFCF diet with standard of care(From enrolment to 6 months)
- To assess the adverse effect profile in children aged 3 - 8 years with ASD receiving add-on LGIT, MAD and GFCF diet with standard of care.(From enrolment to 6 months)
研究者
Sheffali Gulati
Dr Sheffali Gulati
All India Institute of Medical Sciences