A clinical trial to Evaluate Efficacy and Safety of Traditional Indian Medicine (TIM) of Siddha formulations in Children with Autism.

Not Applicable

Completed

Conditions: Mental, Behavioral and Neurodevelopmental disorders, (2) ICD-10 Condition: F989||Unspecified behavioral and emotional disorders with onset usually occurring in childhood and adolescence,

Registration Number: CTRI/2020/09/028149

Lead Sponsor: Manushyaa Blossom Private limited

Brief Summary: 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.

StudyOverview:

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

The duration of each patientâ€™s participation in the study will be of 96days. Scheduled study visits will include:

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

Â·        Visit 2 (Telephonicvisit, Day 24)

Â·        Visit 3 (Day 48)

Â·        Visit 4 (Telephonicvisit, Day 72)

Â·        Visit 5 (End ofstudy visit, Day 96)

During Visit 1 (Screening/ enrollment/ baseline visit, Day 0), informed consent will be obtained from childrenâ€™sparents/caretakers/guardians before any study procedures take place. Afterpatient has been consented, medical history will then be documented, includingthe concomitant medications. All patients will undergo the screening procedureby 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 signswill be recorded. Routine laboratory tests will be done. Subjective assessment ofthe diseases will be done by the investigator using ISAA questionnaire. Patientâ€™scaretakers will be given enough quantity of study medications sufficient tillthe next site visit as per randomization schedule. Parents/ guardians will begiven dosing instructions*. (Please refer section 10.2 for detaileddosing)* Patients diaries will be given to the caretakers/ guardians.They will be asked to record the dosing details along with adverse events (ifany) experienced and concomitant medication taken by the patient. Patients will be given instructions for the nextvisit.

During Visit 2,telephonic visit, patientâ€™s parents/ caretakers will be contacted telephonicallyon Day 24. They will be asked about the adverse events or any other problemand concomitant medications.

At Visit 3 (Day 48), parents/ guardiansare required to get their patient diaries for review. Patients will visit the siteon Day 48. The guardians should return the used as well as unused study medicationsto check the adherence to treatment. They will be asked about adverse eventsand concomitant medication (if any). Patientâ€™s physical examination including vitalsigns will be recorded. Their demographic parameters (height, weight andcircumference of head) will be recorded. The investigator will do the assessmentof the disease using ISAA questionnaire. Investigator will do global evaluationof the disease by Clinical Global Impression (CGI) scale. Patientâ€™s caretakerswill be instructed for the next visit. They will be given enough quantity ofthe study drug sufficient till the next site visit.

During Visit4, telephonic visit, patientâ€™s parents/ caretakers will be contactedtelephonically on Day 72. They will be asked about the adverse events orany 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 willvisit the site. The guardians should return the used as well as unopenedpackages to check the adherence to treatment. They will be asked about adverseevents and concomitant medication (if any). Patientâ€™s vital signs and demographicparameters (height, weight and circumference of head) will be recorded Patientâ€™sphysical examination including vital signs will be recorded. Their demographic parameters(height, weight and circumference of head) will be recorded. The investigator willdo the assessment of the disease using ISAA questionnaire. He will do globalevaluation 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 2days after the scheduled date of the visit in case of any valid reason.*

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 32

Inclusion Criteria

Patients with DSM-V diagnosis of Autistic Disorder 2.
Male or female patients Ëƒ 5 years and Ë‚ 17 years of age 3.
Patients with weight Ëƒ 15 kg 4.
Patients on anticonvulsants used for treatment of seizure disorder with the dosage has been stable for 4 weeks and patient seizure free for at least 6 months 5.
Clinical Global Impression Severity score of at least 4 6.
Patients living with parents or caretaker 7.
Patients whose parents are willing to give free written consent 8.
Patients with language, hearing and vision compatible with the study measurements as judged by the investigator 9.
No allergies to any of the ingredients of the study drug 10.
Patients having no allergy to sulpha drugs 11.
Patient are willing to follow the protocols requirements.

Exclusion Criteria

Patients below the age Ë‚ 5 years and Ëƒ 17 years of age 2.
Patients with IQ below 18 months 4.
Patients with an evidence of hypersensitivity to any of study product components 5.
Patents with DSM-V diagnosis of Pervasive Developmental Disorder other than Autistic Disorder 7.
Patients with a significant concomitant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder 8.
Patients with weight less than 15 kg 9.
Patients requiring initiation of a major change in psychosocial intervention (including investigational) within 4 weeks prior to screening 10.
Patients with a risk of suicidal behavior 11.
Patients with medical history of alcohol or substance abuse/dependence 12.
Patient has participated in another clinical study involving another investigational agent within 4 weeks of the start of this trial, or is planning participation in another clinical trial during the current study duration 13.
Patients with presence of any symptom indicating serious or malignant disease 15.
Patient having a Medical or social condition that would, in the opinion of the investigator, place the subject at an unacceptable risk or render the subject unable to meet the requirements of the protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Mean change in Indian Scale for Assessment of Autism (ISAA) score from baseline (Screening/ enrollment/ baseline visit, Day 0) to the end of the treatment	Mean change in Indian Scale for Assessment of Autism (ISAA) score from baseline (Screening/ enrollment/ baseline visit, Day 0) to the end of the treatment

Secondary Outcome Measures

Name	Time	Method
Treatment emergent adverse events (TEAEs).	Change in the Clinical Global Impression (CGI) score at the end of the treatment

Trial Locations

Locations (4): F.S Endocrine & Diabetic Center
🇮🇳
Hyderabad, TELANGANA, India
Health Point Hospital
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Kolkata, WEST BENGAL, India
Mahatma Gandhi Medical College& Research Institute
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Pondicherry, PONDICHERRY, India
Parul Institute of Ayurved and Parul Ayurveda Hospital
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Vadodara, GUJARAT, India
F.S Endocrine & Diabetic Center
🇮🇳Hyderabad, TELANGANA, India
Dr Vibhuti Narayan Mishra
Principal investigator
7731030321
investigator@ishnovaclinical.com