Efficacy of MAD as add-on Therapy in Comparison With Standard of Care in Children With ASD

NCT ID: NCT06315465

Last Updated: 2024-03-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-20
• Study Completion Date: 2026-01-01

Brief Summary

In general ketogenic diet is a recognized as an efficient non pharmacological treatment for children with refractory epilepsy. However, in the last decade, it has been tried for many neurological disorders in children including ASD, neurodegenerative disorders.

Studies have shown that KD also helps in improvement of cognition, social skills, language function, and stereotypies. There is a limited number of reports of improvements after KD treatment, was insufficient evidence to attest the practicability of the KD as a treatment for ASD, but it is still a good indicator that this diet is a promising therapeutic option for this disorder. There are no major RCT's, hence raises concerns about the reliability and generalizability of findings. Majority of studies have used combined ketogenic diet therapy rather than single diet therapy and not many studies have compared add-on dietary intervention with standard of care. When compared to classic KD diet Modified Atkin's Diet is less restrictive, more palatable, more feasible and early response can be achieved. In summary, the rationale for conducting this study lies in the importance of add on dietary therapy in form of Modified Atkin's Diet along with standard of care for improvement of behavioral symptoms in children with ASD aged 3-8 years.

This study aims to provide valuable insights that it can improve behavioral symptoms in ASD, early and ultimately improve the developmental outcomes in these children.

Detailed Description

• All the children presenting to Paediatrics OPD and Autism clinic in the Child Neurology division will be screened and those fulfilling the inclusion and exclusion criteria will be enrolled into the study
• Informed consent will be taken from parents for the study
• Baseline demographic details and following evaluation will be done -

1. Autism severity assessment using CARS -2, ABC

2. Neurocognitive assessment using (DQ/IQ/SQ) -VSMS

3. Behavioral assessment using CBCL

4. Sleep related issues using CSHQ After initial assessment children are randomized into Group I and Group II using computer generated random numbers.

Group I-Modified Atkin's Diet with standard of care arm

• Group I will receive Modified Atkin's Diet with standard of care whereas Group II will receive standard of care alone.
• Children randomized into Group I, initial workup for Modified Atkin's Diet will be done in the form of Electrocardiogram, Renal Function Tests, Liver Function Tests, Complete Blood Counts, Lipid profile, Urine calcium creatinine ratio and Ultrasound Pelvis for nephrocalcinosis. If pre KD work up is normal, then Modified Atkin's Diet will be initiated in the ratio of 1:1.
• Urine ketones will be checked daily using ketone dipsticks
• Telephonic contacts will be made in regular intervals every week to further ensure compliance at home, and to ensure proper understanding and confidence of parents
• Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy, will be considered as deviates
• First follow-up will be at 4 weeks of treatment initiation, followed by at 8, 12, 16, 20 and 24 weeks
• Compliance rate and adverse events will also be calculated from patient diary/log
• Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy, will be considered as deviates
• First follow-up will be at 4 weeks of treatment initiation, followed by at 8, 12, 16, 20 and 24 weeks
• Compliance rate and adverse events will also be calculated from patient diary/log
• Every alternate subject from each category, pre - intervention f MRI and 3 months post intervention f MRI is done (total 10 subjects) Group II -Standard of care arm
• Standard of care intervention plan will be devised for each subject based on the principles of -
• Behavioral therapy

1. Behavioral modification techniques

2. Psycho education

3. Cognitive behavioral therapy

4. Activity based interventions like eye contact exercises, attention enhancement exercises, self-help skills

5. Speech therapy

6. Parental training

• Occupational therapy
• Sensory integration therapy
• Pharmacotherapy - Anti-psychotic medications
• The parents of the children will be called telephonically every weekly to check for any issues and reinforcement to ensure appropriate regular behavioural intervention to be provided to the child.
• Physical follow up - 4, 8, 12, 16, 20, 24 weeks
• Follow up assessments - 12 weeks (3 months) & 24 weeks (6 months)

Functional MRI acquisition Every 4th subject from each group who provide consent for doing a f-MRI, will undergo a pre-intervention f-MRI and post-intervention f-MRI at 3 months follow-up (10 subjects in each arm, i.e. 20 subjects) These investigations would be done free of cost for the patients. The data will be compared with fMRI data of controls (retrospective data of children with dyslexia who received AI enabled-remedial intervention alone (for 6 weeks) as a part of a previous study by Dr Sayoni Roy Chowdhary, under the guidance of Prof Sheffali Gulati as Chief guide, after ethical clearance). The data will also be compared with the historical data of typical readers, acquired using the same f-MRI protocol at our center

Conditions

Modified Atkins Diet; Autism Spectrum Disorder; Standard of Care

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Modified Atkin's diet with standard of care arm

Group I will receive Modified Atkin's Diet with standard of care whereas Group II will receive standard of care alone. Children randomized into Group I, initial workup for Modified Atkin's Diet will be done in the form of Electrocardiogram, Renal Function Tests, Liver Function Tests, Complete Blood Counts, Lipid profile, Urine calcium creatinine ratio and Ultrasound Pelvis for nephrocalcinosis. If pre KD work up is normal, then Modified Atkin's Diet will be initiated in the ratio of 1:1.Urine ketones will be checked daily using ketone dipsticks. Telephonic contacts will be made in regular intervals every week to further ensure compliance at home, and to ensure proper understanding and confidence of parents. Those children who are unable to tolerate taking adequate ketogenic diet therapy requiring discontinuation of therapy, will be considered as deviates. First follow-up will be at 4 weeks of treatment initiation, followed by at 8, 12, 16, 20 and 24 weeks.

Group Type: EXPERIMENTAL

Modified Atkin's Diet with standard of care

Intervention Type: DIETARY_SUPPLEMENT

children who have given their consent and are randomized into Group I arm receives Modified Atkins Diet along with standard of care after completion of baseline investigations. Modified Atkin's Diet will be started in ratio of 1:1 and compliance is monitored by urine ketones. Followup will be done telephonically to check for compliance , adverse events at every 4 week intervals till 24 weeks.

Standard of Care

Intervention Type: OTHER

Standard of care intervention plan will be devised for each subject which includes Behavioral therapy , Psychoeducation, Activity based interventions like attention enhancement exercises, self help skills, Occupational therapy, Pharmacotherapy, Sensory integration therapy. The parents of the children will be called telephonically every weekly to check for any issues and reinforcement to ensure appropriate regular behavioral intervention to be provided to the child. Physical follow up will be done every 4 weekly till 24 weeks.

Standard of care arm

• Standard of care intervention plan will be devised for each subject based on the principles of -
• Behavioral therapy

1. Behavioral modification techniques

2. Psycho education

3. Cognitive behavioral therapy

4. Activity based interventions like eye contact exercises, attention enhancement exercises, self-help skills

5. Speech therapy

6. Parental training

• Occupational therapy
• Sensory integration therapy
• Pharmacotherapy - Anti-psychotic medications
• The parents of the children will be called telephonically every weekly to check for any issues and reinforcement to ensure appropriate regular behavioural intervention to be provided to the child.
• Physical follow up - 4, 8, 12, 16, 20, 24 weeks
• Follow up assessments - 12 weeks (3 months) & 24 weeks (6 months)

Group Type: OTHER

Standard of Care

Intervention Type: OTHER

Standard of care intervention plan will be devised for each subject which includes Behavioral therapy , Psychoeducation, Activity based interventions like attention enhancement exercises, self help skills, Occupational therapy, Pharmacotherapy, Sensory integration therapy. The parents of the children will be called telephonically every weekly to check for any issues and reinforcement to ensure appropriate regular behavioral intervention to be provided to the child. Physical follow up will be done every 4 weekly till 24 weeks.

Interventions

Modified Atkin's Diet with standard of care

children who have given their consent and are randomized into Group I arm receives Modified Atkins Diet along with standard of care after completion of baseline investigations. Modified Atkin's Diet will be started in ratio of 1:1 and compliance is monitored by urine ketones. Followup will be done telephonically to check for compliance , adverse events at every 4 week intervals till 24 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Standard of Care

Standard of care intervention plan will be devised for each subject which includes Behavioral therapy , Psychoeducation, Activity based interventions like attention enhancement exercises, self help skills, Occupational therapy, Pharmacotherapy, Sensory integration therapy. The parents of the children will be called telephonically every weekly to check for any issues and reinforcement to ensure appropriate regular behavioral intervention to be provided to the child. Physical follow up will be done every 4 weekly till 24 weeks.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 1. Children aged 3 to 8 years diagnosed with Autism Spectrum Disorder according to DSM -V criteria

Exclusion Criteria

1. Diagnosed genetic and metabolic syndromes

2. Pre-existing food fads

3. Associated seizure disorder/epilepsy syndrome

4. Chronic systemic illness

5. Received any form of dietary therapy in the previous 6 months

6. Not on stable standard of care therapy or changes in antipsychotic medications over the last 1 month

7. Refusal of consent

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

All India Institute of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Sheffali Gulati

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sheffali Gulati, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Central Contacts

Sheffali Gulati, MD

Role: CONTACT

sheffaligulati@gmail.com

01126594679

Sheffali Gulati, MD

Role: CONTACT

sheffaligulati1@gmail.com

9810386847

Other Identifiers

AIIMSA00647

Identifier Type: -

Identifier Source: org_study_id