| CTRI Number |
CTRI/2024/07/070353 [Registered on: 10/07/2024] Trial Registered Prospectively |
| Last Modified On: |
08/07/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Nutraceutical |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
To study the effect of ACETYL-L-CARNITINE as supplement
in Clozapine resistant Schizophrenia
|
|
Scientific Title of Study
|
ACETYL-L-CARNITINE as augmentation therapy
in Clozapine resistant Schizophrenia
|
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Dilsohoj Kaur |
| Designation |
Post-graduate Student, Department of Psychiatry Rajindra Hospital, Patiala. |
| Affiliation |
Rajindra Hospital, Patiala. |
| Address |
Department of Psychiatry, Government Medical College, Rajindra Hospital Patiala
Patiala
PUNJAB
147001
India |
| Phone |
8699245736 |
| Fax |
|
| Email |
dilsohoj19@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Rajnish Raj |
| Designation |
Professor and Head, Department of Psychiatry Rajindra Hospital, Patiala. |
| Affiliation |
Rajindra Hospital Patiala |
| Address |
Department of Psychiatry, Government Medical College, Rajindra Hospital Patiala
Patiala
PUNJAB
147001
India |
| Phone |
9814913599 |
| Fax |
|
| Email |
drrajnishraj03@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Dilsohoj Kaur |
| Designation |
Post-graduate Student, Department of Psychiatry Rajindra Hospital, Patiala. |
| Affiliation |
Rajindra Hospital Patiala |
| Address |
Department of Psychiatry, Government Medical College, Rajindra Hospital Patiala
Patiala
PUNJAB
147001
India |
| Phone |
8699245736 |
| Fax |
|
| Email |
dilsohoj19@gmail.com |
|
|
Source of Monetary or Material Support
|
| Dr Dilsohoj Kaur,Department of Psychiatry,Government Medical College, Rajindra Hospital,Patiala, Punjab,India, Pincode-143001 |
|
|
Primary Sponsor
|
| Name |
Government Medical College Patiala |
| Address |
Department of Psychiatry, Government Medical College, Rajindra Hospital, Patiala, Punjab, India, Pincode-143001 |
| Type of Sponsor |
Government medical college |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Dilsohoj Kaur |
Rajindra Hospital Patiala |
Department of Psychiatry,OPD Block-Room no. 1,2 and IPD - Ward no.18
Patiala
PUNJAB |
8699245736
dilsohoj19@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Research and Ethics Committee GMC Patiala |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: F20||Schizophrenia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
ACETYL-L-CARNITINE AS AUGMENTATION THERAPY IN CLOZAPINE RESISTANT SCHIZOPHRENIA |
Schizophrenia is a chronic disorder associated with wide range of manifestations in several psychopathological dimensions such as positive, negative, disorganized, cognitive and affective symptoms. Up to 2/3rd of patients achieve good outcomes with antipsychotic treatment whereas 1/3rd show poor outcome. Thus, 30% to 40% of patients have Treatment Resistant
Schizophrenia (TRS) characterized by inadequate response to treatment with two or more trials of dopaminergic antipsychotics (more than 600 chlorpromazine equivalents); and illness duration more than 2 years. The antipsychotic Clozapine is the drug of choice for management of TRS. Many patients however do not respond to Clozapine monotherapy and require to be administered adjunctive treatments. They have high risk of bioenergetic and cognitive dysfunction. Acetyl-L-carnitine is involved in the bioenergetic pathways and it may be beneficial in cognitive dysfunction. The aim of the study is to assess therapeutic efficacy of Acetyl-L-Carnitine as an
augmenting agent in clozapine resistant schizophrenia. 78 participants will be recruited using consecutive purposing
sampling in a hospital based prospective, parallel group, open label study. Group I (39) will be given clozapine plus minus other antipsychotics plus acetyl L carnitine and Group II (9) will be given clozapine plus minus other antipsychotics plus placebo. The sociodemographic and clinical data will be recorded. Primary outcomes of treatment(efficacy of treatment as assessed by severity of symptoms and functioning) will be assessed on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions Scale (CGI), Global Assessment of Functioning (GAF) and Montreal Cognitive Assessment (MoCA).
Secondary outcomes will be assessed for antipsychotic side effects on Abnormal Involuntary Movement Scale (AIMS) and
Barnes Akathisia Rating Scale (BARS), adverse drug effects of ALC on adverse event scale and cost effectiveness. Data
thus extracted will be analyzed by appropriate statistical methods with P value ≤0.05 being statistically significant.
|
| Comparator Agent |
Placebo |
The total duration of intervention is 12 weeks. The antipsychotic Clozapine is the drug of choice for management of TRS. Many patients however do not respond to Clozapine monotherapy and require to be administered adjunctive treatments. They have high risk of bioenergetic and cognitive dysfunction. Acetyl-L-carnitine is involved in the bioenergetic pathways and it may be beneficial in cognitive dysfunction. The aim of the study is to assess therapeutic efficacy of Acetyl-L-Carnitine as an augmenting agent in clozapine resistant schizophrenia. 78 participants will be recruited using consecutive purposing sampling in a hospital based prospective, parallel group, open label study. Group I (39) will be given clozapine plus minus other antipsychotics plus acetyl L carnitine and Group II (9) will be given clozapine plus minus other antipsychotics plus placebo. The sociodemographic and clinical data will be recorded. Primary and secondary outcomes accessed at 4,8 and 12 weeks. Data thus extracted will be analyzed by appropriate statistical methods with P value ≤0.05 being statistically significant |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
INCLUSION CRITERIA
1. Patients (Male & Female) in the age group of 18 to 60 years.
2. Patients suffering from schizophrenia as per ICD-11.
3. Patients who fulfilled the criteria for TRS will be selected for study.
For the purpose of the study treatment resistant schizophrenia is
defined as:[26]
a. Failure to respond to ≥ 2 antipsychotic.
b. Treatment failure of ≥1 antipsychotic + prospective treatment failure
with another antipsychotic (different from the one previously failed).
c. Dose and duration: each treatment with > 600 chlorpromazine
equivalents per day for > 6 weeks.
d. Lack of improvement in a reducing CGI > 4 and GAF < 50.
e. The duration of illness should be at least two years.
f. In addition, the patients should be resistant to clozapine provided at
adequate dose for an adequate duration.
4. Medically stable patient will be included.
5. Patients who will be accompanied by reliable informants.
6. Patients and informants who willingly participate in the study and take
ALC as augmentation therapy for TRS.
7. Patients giving written informed consent will be included. |
|
| ExclusionCriteria |
| Details |
EXCLUSION CRITERIA
The patients with following characteristics were excluded from study:
1. Patients who have associated medical problems, which could affect the course of illness. eg. cerebrovascular diseases, renal diseases,
pulmonary disease etc.
2. Patients of co-morbid alcohol and substance use disorder except nicotine.
3. Pregnant and breastfeeding females.
4. Violent unmanageable patients.
5. Intellectual disability patients.
6. Patients unable to cooperate on test of MoCA on first followup will be considered non eligible.
7. Patients hypersensitive to ALC. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Improvement in illness severity
PANSS Score
CGI Score
1. Improvement in Cognition MoCA Score
2. Improvement in global functioning GAF Score
3. Treatment response : Defined as fall in CGI score to ≤2 or fall of
greater than or equal to 20% score on PANSS. |
Follow-up assessment for primary and secondary
outcomes will be done at baseline, 4-weeks, 8-weeks and 12-weeks. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1.Improvement in antipsychotic side effects on AIMS and BARS scales
2.Adverse event scale
3.Cost effectiveness inventory
|
Follow-up assessment for primary and secondary
outcomes will be done at baseline, 4-weeks, 8-weeks and 12-weeks. |
|
|
Target Sample Size
|
Total Sample Size="78"
Sample Size from India="78"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
20/07/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Schizophrenia is a chronic disorder associated with wide range of manifestations in several psychopathological dimensions such as positive, negative, disorganized, cognitive and affective symptoms. Up to 2/3rd of patients achieve good outcomes with antipsychotic treatment whereas 1/3rd show poor outcome. Thus, 30% to 40% of patients have Treatment Resistant Schizophrenia (TRS) characterized by inadequate response to treatment with two or more trials of dopaminergic antipsychotics (> 600 chlorpromazine equivalents); and illness duration more than 2 years. The antipsychotic Clozapine is the drug of choice for management of TRS. Many patients however do not respond to Clozapine monotherapy and require to be administered adjunctive treatments. They have high risk of bioenergetic and cognitive dysfunction. Acetyl-L-carnitine is involved in the bioenergetic pathways and it may be beneficial in cognitive dysfunction. The aim of the study is to assess therapeutic efficacy of Acetyl-L-Carnitine as an augmenting agent in clozapine resistant schizophrenia. 78 participants will be recruited using consecutive purposing sampling in a hospital based prospective, parallel group, open label study. Group I (n=39) will be given clozapine ± other antipsychotics + acetyl-L-carnitine and Group II (n=39) will be given clozapine ± other antipsychotics + placebo. The sociodemographic and clinical data will be recorded. Primary outcomes of treatment (efficacy of treatment as assessed by severity of symptoms and functioning) will be assessed on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions Scale (CGI), Global Assessment of Functioning (GAF) and Montreal Cognitive Assessment (MoCA). Secondary outcomes will be assessed for antipsychotic side effects on Abnormal Involuntary Movement Scale (AIMS) and Barnes Akathisia Rating Scale (BARS), adverse drug effects of ALC on adverse event scale and cost effectiveness. Data thus extracted will be analyzed by appropriate statistical methods with P value ≤0.05 being statistically significant. |