INTRODUCTION and background:

The core features of autism spectrum disorder (ASD) are persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, or activities.¹ According to estimates from Center for Disease Control and Prevention (CDC) data approximately 1 in 68 children has been identified with ASD. Studies in North America, Asia, and Europe have reported the average prevalence of individuals with autism as between 1% and 2%. ² ASD is a lifelong condition of rising prevalence and community concern. The etiology of ASD is still controversial; various hypotheses concerning genetics, environmental factors, neurobiological factors, and neuropathology have been proffered.³ There are many different types of treatment for ASD, such as medication management, education, rehabilitation training, sensory integration, and dietary approaches. In the traditional Chinese medicine (TCM) terms, the highest frequency of symptoms used to diagnose autism are "dullness", "mutistic", "soliloquy", "five kinds of retardation", "five weaknesses", "fetal toxicity" and "infantile metopism". By consulting ancient books and monographs, we found TCM associated with treatment of the aforementioned autism descriptors used by TCM. Although there are no treatments for the core features of ASD, certain medications and behavioral therapies have been identified for the management of hyperactivity, depression, inattention, or seizures.^4,5 Among the pharmacologic interventions, risperidone is the most commonly used treatment for serious behavioral symptoms in children with autism.⁶ Despite its beneficial effects on behavioral problems, the results of risperidone treatment are inconclusive and have been associated with adverse events, such as increased appetite, rhinorrhea, somnolence, and excessive weight gain.⁷ The parents of children with ASD are therefore concerned about potential adverse drug effects and are seeking treatments that are more secure. The volume of research into herbal medicines, a form of Complementary and Alternative Medicine (CAM), with fewer adverse effects, has increased for the treatment of children with ASD.

Rationale for conducting this study:

Traditional Indian Medicine (TIM) of Siddha is one of the oldest medical system in the world which is believed to be originated more than 10,000 years ago in India, now widely practiced in Tamil Nadu. Traditional Indian Medicine (TIM) of Siddha classifies disease and disorders into 4448 types. While accepting its benefits global community demands evidence based scientific explanation to understand the concept of Siddha medicine and demands quality matching International standards to reassure the efficacy of Siddha medicine.

At present, the incidence of Manthasanni (Autism spectrum disorder), is rising, but the effect of treatment and prognosis are still not satisfactory. There is an increasing prevalence and its impact in reducing the quality of life in children is the reason to choose an efficient and nutritive drug which is believed to good in central nervous system. The main aim of Siddha is to assure a healthy life to mankind. 

The present study will be conducted on ASD to see the improvement in the quality of life by employing the Siddha therapeutic formulations and procedures. All the ingredients in both Internal and External medicines are herbal and mineral combinations.

This is a prospective, open label, multi-center, clinical follow-up study of 32 children with autism aimed at evaluating the safety and efficacy of two siddha formulations.

Study Overview:

Thirty-two patients (children) with autism selected from OPD of the designated hospitals (sites) will be included in this multi-center, double arm study. Patients will complete a screening to determine eligibility for the study based on Inclusion & Exclusion Criteria, patient history and safety measures.

The duration of each patient’s participation in the study will be of 96 days. Scheduled study visits will include:

·         Visit 1 (Screening/ enrollment/ baseline visit, Day 0)

·         Visit 2 (Telephonic visit, Day 24)

·         Visit 3 (Day 48)

·         Visit 4 (Telephonic visit, Day 72)

·         Visit 5 (End of study visit, Day 96)

During Visit 1 (Screening/ enrollment/ baseline visit, Day 0), informed consent will be obtained from children’s parents/caretakers/guardians before any study procedures take place. After patient has been consented, medical history will then be documented, including the concomitant medications. All patients will undergo the screening procedure by inclusion and exclusion criteria. Demography (Date of birth, age, place of birth, time of birth nature of delivery (normal/ cesarean), age, sex, race, height, weight and circumference of head), physical examination including vital signs will be recorded. Routine laboratory tests will be done. Subjective assessment of the diseases will be done by the investigator using ISAA questionnaire. Patient’s caretakers will be given enough quantity of study medications sufficient till the next site visit as per randomization schedule. Parents/ guardians will be given dosing instructions. (Please refer section 10.2 for detailed dosing) Patients diaries will be given to the caretakers/ guardians. They will be asked to record the dosing details along with adverse events (if any) experienced and concomitant medication taken by the patient.  Patients will be given instructions for the next visit.   

During Visit 2, telephonic visit, patient’s parents/ caretakers will be contacted telephonically on Day 24. They will be asked about the adverse events or any other problem and concomitant medications.

At Visit 3 (Day 48), parents/ guardians are required to get their patient diaries for review. Patients will visit the site on Day 48. The guardians should return the used as well as unused study medications to check the adherence to treatment. They will be asked about adverse events and concomitant medication (if any). Patient’s physical examination including vital signs will be recorded. Their demographic parameters (height, weight and circumference of head) will be recorded. The investigator will do the assessment of the disease using ISAA questionnaire. Investigator will do global evaluation of the disease by Clinical Global Impression (CGI) scale. Patient’s caretakers will be instructed for the next visit. They will be given enough quantity of the study drug sufficient till the next site visit.  

During Visit 4, telephonic visit, patient’s parents/ caretakers will be contacted telephonically on Day 72. They will be asked about the adverse events or any other problem and concomitant medications.

At Visit 5 (End of study, Day 96), parents/ guardians are required to get their patient diaries for review. Patients will visit the site. The guardians should return the used as well as unopened packages to check the adherence to treatment. They will be asked about adverse events and concomitant medication (if any). Patient’s vital signs and demographic parameters (height, weight and circumference of head) will be recorded Patient’s physical examination including vital signs will be recorded. Their demographic parameters (height, weight and circumference of head) will be recorded. The investigator will do the assessment of the disease using ISAA questionnaire. He will do global evaluation of the disease by Clinical Global Impression (CGI).  

Note: For Visit 3 and 5, patients can visit the site within maximum 2 days before or 2 days after the scheduled date of the visit in case of any valid reason.