Effect of Increasing Total Antioxidant Capacity in Autism Spectrum Disorder (TACASD)

October 2, 2024 updated by: Rinvil Renaldi

Randomized, Placebo-controlled, Double-blind Study of Increasing Total Antioxidant Capacity with Vitamin E and C in Two Cohorts of Patients with Autism Spectrum Disorders

This double-blind, randomized, controlled trial (RCT) has the aim to evaluating the effectiveness of increasing Total Antioxidant Capacity (TAC) as add-on intervention in two cohorts of patients with Autism Spectrum Disorder (ASD) who have received Risperidone (0.02-0.06 mg/KgBW) and Behavior Therapy as maintenance therapy. Both groups will receive placebo pill or Vitamin E and C pill using randomization. Clinical Symptoms, Aberrant Behavior and Quality of Life in Children with ASD will be assessed after 12 weeks of treatment in this study. Primary outcome measures of efficacy is Aberrant Behavior Checklist- Irritability (ABC-Irritability) and Secondary outcome measures include Childhood Autism Rating Scale (CARS), Clinical Global Impression Scale - Improvement (CGI-I), The PedsQL and The WHOQOL BREF.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The continuation of ASD throughout life makes all efforts to optimize the abilities of children with ASD as early as possible so that their quality of life becomes better important. Management to improve current symptoms and overcome aberrant behavior in children with ASD generally focuses on behavioral intervention, psychotherapy and even pharmacotherapy, but the results are not satisfactory because it takes time, is expensive and unexpected side effects often occur after administering pharmacotherapy. On the other hand, research related to the role of oxidative stress has suggested a potential relationship between oxidative stress and autism pathophysiology that is not correlated with age and the underlying pathogenesis, but damage caused by oxidative stress will exacerbate dysfunction in children with ASD through chronic inflammatory responses, DNA and protein damage and mitochondrial superoxide production. Oxidative stress will influence the clinical symptoms and pathogenesis of ASD. Therefore, efforts to control the balance of oxidative stress to improve symptoms and neuropsychological deficits in patients with ASD are important. Lack of antioxidant capacity in children with ASD to neutralize and remove oxidants has been associated with the severity of clinical symptoms and aberrant behavior in children with ASD. Therefore, efforts to increase antioxidant capacity through providing antioxidants can offer a new strategy for dealing with accompanying symptoms in children with ASD.

Vitamin E and Vitamin C are non-enzymatic antioxidants which function to strengthen the work of enzymatic antioxidants in the oxidant-elimination, oxidation-reduction cycle process that occurs in the brain. Its includes in group of antioxidants which also referred as chain breaking. When used together with vitamin C which can function as a water-soluble antioxidant and other enzyme cofactors, reduced vitamin C can directly regenerate vitamin E which simultaneously undergoes oxidation to become ascorbate. Therefore, the use of vitamin C will be more effective when used together with vitamin E. Research has shown that administration with antioxidants such as vitamin E and vitamin C has a good effect on clinical symptoms and behavior in children with ASD.

In this randomized controlled trial (RCT), patients with Autism Spectrum Disorder (ASD) who have received Risperidone and Behavior Therapy as maintenance therapy will be randomly assigned to receive either a placebo or a combination of Vitamins E (150-200 IU per day) and C (100-200 mg per day) for a duration of 3 months. This study was designed to verify whether increasing the TAC using Vitamin E and C improves clinical symptoms, aberrant behaviors, and quality of life in children with ASD.

This study shall include 50 patients with ASD, aged 3-9 years old. The study design of this RCT was balanced to all of patients treated with maintenance therapy as usual, so that half of the patients will receive placebo, and the remaining half will receive Vitamin E and C during 3 months. The purpose is to observe whether the increase of TAC could improve the clinical symptoms, aberrant behavior and quality of life in ASD patients. In addition to clinical and psychometric parameters, TAC will be measured at baseline, after 6 weeks and 12 weeks, by collecting 30-60 ml of fresh urine, a general urinalysis examination to rule out acute urinary tract infections, The TAC examination is carried out when the urine pH is normal and measurement with a calorimetric kit with enzyme method, ABTS.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • South Sulawesi
      • Makassar, South Sulawesi, Indonesia
        • Doctoral Programme at Hasanuddin University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Both parents or a legally authorized patient representative (LAR) must provide written informed consent. The parents and guardian must be able to understand and comply with the experimental protocol with a minimum of junior high school education.
  2. Parents earn no less than IDR 3,434,298 (South Sulawesi Province Minimum Wage for 2024).
  3. Subjects of both sexes, aged between 3-9 years old, may be included in the study.
  4. The subject must meet DSM-5 criteria for a primary diagnosis of Autism.
  5. Patients treated with Risperidone (0.02-0.06 mg/KgBW) are enrolled only if the treatment and dosage of these drugs has been constant for at least 2 months prior to enrollment in the trial and is kept constant throughout the 3-month duration of the trial.
  6. Patients undergoing any kind of behavioral intervention must have must have underwent the intervention at least 2 sessions prior to enrollment and the intervention must remain unchanged throughout the 3-month duration of the trial.
  7. Baseline Clinical Global Impression - Severity (CGI-S) score below 7.
  8. The patient is able to swallow the capsule or his/her parents are available to open it and administer immediately its content in a small quantity of juice or soft-drink.

Exclusion Criteria:

  1. Patients with organic disease and/or congenital malformation including known genetic syndromes for example, Rett syndrome, fragile-X syndrome, and Down Syndrome etc.).
  2. Patients with autism secondary to epileptic encephalopathy or with idiopathic autism co-morbid with seizures more frequent than one episode every 6 months despite ongoing anti epileptic drug therapy.
  3. Patients treated with anticoagulants.
  4. Patients with serious medical illnesses (chronic renal disease, severe liver disease, cardiovascular disorders, malignant tumors, HIV infection).
  5. Patients with a history of acute cerebrovascular episodes.
  6. Patients with a history of stomach bleeding or active peptic ulcer.
  7. Patients with documented allergy, hypersensitivity or intolerance to one of the excipients of the experimental or comparative product.
  8. Patients have been consuming other antioxidants.
  9. Patients with active urinary tract infections.
  10. Patients with poor compliance and or no control back to the Hospital.

Trial interruption criteria:

  1. Patients whose medical conditions require starting treatment with anticoagulants.
  2. Patients with severe medical conditions starting during the 3-month duration of the trial.
  3. Patients who undergo a change in psychopharmacological or behavioral treatment during the 3-month duration of the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: ASD Placebo

If the age is up to 4 years old:

• Risperidone (0.02-0.06 mg/KgBW) and Behavior Therapy as maintenance therapy and Capsule Placebo.

If age is above 4 years old:

• Risperidone (0.02-0.06 mg/KgBW) and Behavior Therapy as maintenance therapy and Capsule Placebo.
Dietary supplement: Placebo
Capsule contains substances that are safe, non-active, and commonly used in pharmaceuticals (microcrystalline cellulose) with an appropriate coloring dye and in the active arms, Vitamin E and C. Capsules can be opened and the content drunk or chewed, if children have difficulties with swallowing capsules
Experimental: ASD Active compound

If the age is up to 4 years old:

• Risperidone (0.02-0.06 mg/KgBW) and Behavior Therapy as maintenance therapy and Capsul containing Vitamin E 150 IU and Vitamin C 100 mg.

If age is above 4 years old:

• Risperidone (0.02-0.06 mg/KgBW) and Behavior Therapy as maintenance therapy and Capsul containing Vitamin E 200 IU and Vitamin C 200 mg.
Dietary supplement: Vitamin E and C
Capsule Vitamin E (Natural Vitamin E, d-alpha tocopherol) 150 IU or 200 IU containing also Vitamin C 100 mg or 200 mg b.id depending on age. Capsules can be opened and the content drunk or chewed, if children have difficulties with swallowing capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Aberrant Behavior Checklist - Irritability (ABC-I)
Time Frame: At 0, 6 and 12 weeks duration of trial
An instrument which is used by parents to measure aberrant behavior in children which consists of 15 assessment items with a scale of 0-3 to assess the level of severity. Score between 0-45 with interpretation if score <20, mild; 20-40 moderate; >40, severe irritability.
At 0, 6 and 12 weeks duration of trial

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Childhood Autism Rating Scale (CARS)
Time Frame: At 0, 6 and 12 weeks duration of trial
CARS is an instrument for measuring the severity of signs and symptoms of ASD carried out by experienced clinicians. Score between 15-60 with interpretation if score <30, non-autistic; 30-36.5 mild to moderate autism; 37-60, severe autism.
At 0, 6 and 12 weeks duration of trial
Clinical Global Impression Scale- Improvement (CGI-I)
Time Frame: At 0, 6 and 12 weeks duration of trial
a scale consisting of 7 assessment points used by clinicians to assess the severity of the patient's initial condition, patient improvement/worsening during follow-up and treatment side effects.
At 0, 6 and 12 weeks duration of trial
The Pediatric Quality of Life TM (The PedsQL)
Time Frame: At 0, 6 and 12 weeks duration of trial
An instrument for assessing the quality of life in children related to health conditions, through self-assessment and/or parental observation, which is assessed based on conditions during the last 1 month.
At 0, 6 and 12 weeks duration of trial
WHOQOL-BREF
Time Frame: At 0, 6 and 12 weeks duration of trial
An instrument for assessing parents' quality of life through self-assessment. The WHOQOL is a 26-item instrument consisting of four domains: physical health (7 items), psychological health (6 items), social relationships (3 items), and environmental health (8 items); it also contains QOL and general health items. Each individual item of the WHOQOL-BREF is scored from 1 to 5 on a response scale, which is stipulated as a five-point ordinal scale. The scores are then transformed linearly to a 0-100-scale.
At 0, 6 and 12 weeks duration of trial

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rinvil Renaldi

Collaborators

Indonesia University
University of Modena and Reggio Emilia
RSUP Dr. Wahidin Sudirohusodo

Investigators

  • Principal Investigator: Rinvil Renaldi, MD, Hasanuddin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2024

Primary Completion (Estimated)

January 31, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

September 30, 2024

First Submitted That Met QC Criteria

October 1, 2024

First Posted (Actual)

October 2, 2024

Study Record Updates

Last Update Posted (Actual)

October 4, 2024

Last Update Submitted That Met QC Criteria

October 2, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TAC_Study_ASD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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