Clinical trial NCT03708614: A Study Looking at How Well Children With Autism Spectrum Disorder on Medications Like Having More Protein
Official title: A Feasibility and Acceptability Study of Elevated Protein Dietary Intake for Children Diagnosed With Autism Spectrum Disorder (ASD) While on Atypical Antipsychotic Medication
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder
Atypical antipsychotic medication
Psychotropic medication
Psychotropic-induced weight gain
Controlled energy intake with elevated protein
Dietary intervention
Acceptability
Feasibility
Lead sponsor: Holland Bloorview Kids Rehabilitation Hospital
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized pilot intervention study
Primary purpose: SUPPORTIVE_CARE

Brief summary: Antipsychotic medications are commonly prescribed in children and adults with ASD (Curtin, Jojic \& Bandini, 2014). But weight gain has been known to be one of the less desirable effects of these medications, increasing one's risk for overweight and obesity. Based on experience in Holland Bloorview's Nutrition Clinic, working with a dietitian to follow specific dietary advice, such as having more protein while keeping the amount of calories the same, may be a possible and useful way to limit weight gain.

This study's objective is to evaluate the feasibility (study designs, methods, processes) and acceptability (client/family satisfaction, perceived effectiveness) of a controlled energy diet with elevated protein intake in children and youth with ASD who are currently taking prescribed atypical antipsychotic medication.

Detailed description: The use of psychotropic medication in children and youth with Autism Spectrum Disorder (ASD) to treat symptoms of aggression, irritability and related behavioural problems has become increasingly common in recent years. Data obtained from clinical and nationally representative populations of children demonstrate that approximately 30%-60% of children with ASD are prescribed at least one psychotropic medication, and 10% are prescribed more than three medications at the same time (Curtin, Jojic \& Bandini, 2014).

Weight gain, which is one of the harmful effects of psychotropic medication, is likely one of the most understood risk factors for obesity in children and adults with ASD. In a systematic review and meta-analysis of double-blinded, randomized, controlled trials studying the metabolic adverse effects of atypical antipsychotics in children and adolescents under 18 years of age, risperidone, olanzapine and aripiprazole were associated with statistically significant weight gain compared with placebo (Almandil et al., 2013). Similar findings were reported from a review of literature, using PubMed, on weight gain and increase of BMI among children and adolescents (0-18 years old) treated with antipsychotic medications (Martinez-Ortega et al., 2013).

Although clinical trials with different agents have been conducted in an attempt to address weight gain in individuals on psychotropic medications, no established treatments or preventative measures have been developed to combat psychotropic-induced weight gain (PIWG) to date (Curtin, Jojic \& Bandini, 2014). A review of published literature using PubMed yielded limited and mixed results for using Metformin as the intervention for the treatment in combating PIWG (Anagostou et al., 2016; Handen et al., 2017). Based on clinical experience in Holland Bloorview's Nutrition Clinic, controlled energy intake combined with elevated protein intake (CEEP) may represent an effective and practical strategy for limiting weight gain.

Potential beneficial outcomes associated with protein ingestion include: a) increased satiety, which is being satisfactorily full - protein generally increases satiety to a greater extent than carbohydrate or fat and may facilitate a reduction in energy consumption; b) increased thermogenesis, which is the production of heat in the body - higher protein diets are associated with an increase in thermogenesis, which also influences satiety and increases energy expenditure; and c) maintenance or growth of fat-free mass (muscle) - an elevated protein diet may provide an increase effect on muscle protein synthesis in some individuals, favouring the retention of lean muscle mass while improving metabolic profile (Paddon-Jones et al., 2018).

This study's primary objective is to evaluate the feasibility (study designs, methods, processes) and acceptability (client/family satisfaction, perceived effectiveness) of a controlled energy diet with elevated protein intake in children and youth with ASD who are currently taking prescribed atypical antipsychotic medication.

Children and youth, ages 6-17 years old, with ASD (n=10) on atypical antipsychotic medication will be exposed to specific nutrition recommendations involving CEEP for ten consecutive weeks. Each participant and parent/guardian will work collaboratively with the RD/RA to formulate strategies to slowly increase protein intake in the range of 20-30% of total caloric intake and ensure consistent energy intake. Data will be collected through food records, anthropometric measurements and informal post-intervention interviews to measure the feasibility and acceptability of the study processes and elevated protein dietary changes.

Eligibility criteria: Inclusion Criteria:

1. Child Inclusion Criteria:

   * Diagnosis of ASD
   * Currently taking one or more atypical antipsychotic medication
   * Ages 6-17 years old
   * Enrolment as an active client in a Psychopharmacology Clinic at Holland Bloorview
   * Accepts all food, based on the SOS Feeding Approach: Defining Picky vs. Problem Eaters by Kay Toomey (2017) - has no significant food aversions; will accept new foods on plate, usually can touch or taste; and consumes one or more foods from all food groups, varying in textures
   * Can communicate in English
   * Has access to a telephone
2. Parent/guardian inclusion criteria:

   * Provides care to study participant
   * Can communicate in English
   * Able to complete food records
   * Has access to a telephone

Exclusion Criteria:

a) Child exclusion criteria:

* Medical condition that contradicts elevated protein intake
* Has significant food aversions
* Has any food allergies
* Currently participating in another clinical study that would interfere with anticipated endpoints and outcome measurements

Primary outcomes:
measure: Caloric and protein intake
timeFrame: At the time of study enrolment (week 0) and during week 10 of intervention implementation (week 10)
measure: Pre- (at time of study enrolment) and post-intervention anthropometric measurements
timeFrame: Measured at the time of study enrolment (week 0) and after ten weeks of intervention (week 11), assessed up to 11 weeks
measure: Pre- (at time of study enrolment) and post-intervention anthropometric measurements
timeFrame: Measured at the time of study enrolment (week 0) and after ten weeks of intervention (week 11), assessed up to 11 weeks
measure: Pre- (at time of study enrolment) and post-intervention anthropometric measurements
timeFrame: Measured at the time of study enrolment (week 0) and after ten weeks of following the intervention (week 11), assessed up to 11 weeks
measure: Post-intervention interview with participants and family
timeFrame: Interview (anticipated duration of 60 minutes) will be conducted after week ten of intervention implementation (week 11)
measure: Study feasibility (designs, methods, processes)
timeFrame: During the screening and recruitment process (anticipated duration of 1-1.5 months)
measure: Study feasibility (designs, methods, processes)
timeFrame: Measurements taken at the start of the study during enrolment and at study completion (anticipated duration of 5 months)
measure: Study feasibility (designs, methods, processes)
timeFrame: Measured at the time of study enrolment (week 0) and after ten weeks of intervention (week 11), assessed up to 11 weeks
measure: Study feasibility (designs, methods, processes)
timeFrame: Interview (anticipated duration of 60 minutes) will be conducted after week ten of intervention implementation (week 11)
measure: Study feasibility (designs, methods, processes)
timeFrame: Interview (anticipated duration of 60 minutes) will be conducted after week ten of intervention implementation (week 11)
measure: Study feasibility (designs, methods, processes)
timeFrame: Interview (anticipated duration of 60 minutes) will be conducted after week ten of intervention implementation (week 11)
measure: Study feasibility (designs, methods, processes)
timeFrame: Interview (anticipated duration of 60 minutes) will be conducted after week ten of intervention implementation (week 11)
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Holland Bloorview Kids Rehabilitation Hospital
state: Ontario
Study officials:
affiliation: Holland Bloorview Kids Rehabilitation Hospital
name: Lorry Chen, Honors BSc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Almandil NB, Liu Y, Murray ML, Besag FM, Aitchison KJ, Wong IC. Weight gain and other metabolic adverse effects associated with atypical antipsychotic treatment of children and adolescents: a systematic review and meta-analysis. Paediatr Drugs. 2013 Apr;15(2):139-50. doi: 10.1007/s40272-013-0016-6.
citation: Anagnostou E, Aman MG, Handen BL, Sanders KB, Shui A, Hollway JA, Brian J, Arnold LE, Capano L, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Hadjiyannakis S, Peleg N, Odrobina D, McAuliffe-Bellin S, Zakroysky P, Marler S, Wagner A, Wong T, Macklin EA, Veenstra-VanderWeele J. Metformin for Treatment of Overweight Induced by Atypical Antipsychotic Medication in Young People With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Sep 1;73(9):928-37. doi: 10.1001/jamapsychiatry.2016.1232.
citation: Curtin C, Jojic M, Bandini LG. Obesity in children with autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):93-103. doi: 10.1097/HRP.0000000000000031.
citation: Handen BL, Anagnostou E, Aman MG, Sanders KB, Chan J, Hollway JA, Brian J, Arnold LE, Capano L, Williams C, Hellings JA, Butter E, Mankad D, Tumuluru R, Kettel J, Newsom CR, Peleg N, Odrobina D, McAuliffe-Bellin S, Marler S, Wong T, Wagner A, Hadjiyannakis S, Macklin EA, Veenstra-VanderWeele J. A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension. J Am Acad Child Adolesc Psychiatry. 2017 Oct;56(10):849-856.e6. doi: 10.1016/j.jaac.2017.07.790. Epub 2017 Aug 19.
citation: Martinez-Ortega JM, Funes-Godoy S, Diaz-Atienza F, Gutierrez-Rojas L, Perez-Costillas L, Gurpegui M. Weight gain and increase of body mass index among children and adolescents treated with antipsychotics: a critical review. Eur Child Adolesc Psychiatry. 2013 Aug;22(8):457-79. doi: 10.1007/s00787-013-0399-5. Epub 2013 Mar 17.
citation: Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A, Westerterp-Plantenga M. Protein, weight management, and satiety. Am J Clin Nutr. 2008 May;87(5):1558S-1561S. doi: 10.1093/ajcn/87.5.1558S.