| CTRI Number |
CTRI/2026/04/107270 [Registered on: 01/04/2026] Trial Registered Prospectively |
| Last Modified On: |
22/03/2026 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
An RCT for bipolar depression comparing Lumateperone with olanzapine fluoxetine combination. |
|
Scientific Title of Study
|
A Randomized Controlled Trial to Compare the Efficacy and Safety of Lumateperone Versus Olanzapine-Fluoxetine Combination in the Treatment of Bipolar Depression |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ND/CT21/FF/2023/37407 |
DCGI |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Rohit Guleria |
| Designation |
Junior Resident |
| Affiliation |
AIIMS BATHINDA |
| Address |
department of Psychiatry
1st floor, B block
AIIMS Bathinda
Bathinda
PUNJAB
151001
India |
| Phone |
9728266339 |
| Fax |
|
| Email |
andiamrsg@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr. Jitender Aneja |
| Designation |
Additional Professor |
| Affiliation |
AIIMS BATHINDA |
| Address |
Department of Psychiatry
Room 2217
1st floor, B block
AIIMS BATHINDA
Mandi Dabwali Road, Bathinda
Punjab-151001
Bathinda
PUNJAB
151001
India |
| Phone |
9728266339 |
| Fax |
|
| Email |
anejajitender@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Rohit Guleria |
| Designation |
Junior Resident |
| Affiliation |
AIIMS BATHINDA |
| Address |
Department of Psychiatry
1st floor
B block
AIIMS BATHINDA
Mandi Dabwali Road, Bathinda
Punjab-151001
Bathinda
PUNJAB
151001
India |
| Phone |
9728266339 |
| Fax |
|
| Email |
andiamrsg@gmail.com |
|
|
Source of Monetary or Material Support
|
| AIIMS Bathinda
mandi dabwani road
Bathinda, punjab
pincode 151001
india |
|
|
Primary Sponsor
|
| Name |
AIIMS BATHINDA |
| Address |
AIIMS BATHINDA
mandi dabwali road
Bathinda punjab
151001
india
|
| Type of Sponsor |
Research institution and hospital |
|
|
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 Rohit Guleria |
AIIMS Bathinda |
Department of Psychiatry OPD
1st floor B block
AIIMS Bathinda
Bathinda
PUNJAB |
9728266339
andiamrsg@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee AIIMS BATHINDA |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: F313||Bipolar disorder, current episodedepressed, mild or moderate severity, (2) ICD-10 Condition: F314||Bipolar disorder, current episodedepressed, severe, without psychotic features, (3) ICD-10 Condition: F315||Bipolar disorder, current episodedepressed, severe, with psychotic features, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Lumateperone 42 mg |
Lumateperone, a novel atypical antipsychotic, approved by the US FDA in 2021 for bipolar
depression, acts via multiple mechanisms: 5-HT2A receptor antagonism, dopamine D2
receptor modulation (partial presynaptic agonism and postsynaptic antagonism), and
enhancement of NMDA (N-methyl-D-aspartate) receptor-mediated glutamatergic
neurotransmission via D1 receptor pathways [9,10]. Lumateperone has shown promising
results in reducing depressive symptoms with a more favourable metabolic and
extrapyramidal profile compared to existing treatments [11]. However, no head-to-head
randomized controlled trials exist comparing lumateperone with OFC, an evidence-based
standard. Given the pressing need for effective and well-tolerated alternatives, a direct
comparison using a design will provide critical data to inform clinical decision-making. |
| Comparator Agent |
Olanzapine 5mg Fluoxetine 20mg combination |
current guidelines from the Canadian Network for Mood and Anxiety
Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommend
mood stabilizers or second-generation antipsychotics with proven efficacy in bipolar
depression [5]. One such approved combination is Olanzapine-Fluoxetine Combination
(OFC), which was shown to be superior to placebo and monotherapy with either agent in
multiple randomized trials [6,7]. However, OFC is associated with significant adverse effects
including weight gain, metabolic syndrome, and sedation |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Diagnosed with Bipolar 1/2 disorder, currently in depressive episode as per DSM 5 Criteria
BMI between 18 and 25 km/m2
On stable dose of lithium/valproate for 2 weeks prior
MADRS equal or greater than 20 and YMRS less than 12 |
|
| ExclusionCriteria |
| Details |
1. Known allergy or hypersensitivity to either study medication or their components.
2. Current or past diagnosis of schizophrenia, schizoaffective disorder, or primary
substance use disorder (excluding nicotine) in the past 6 months.
3. Recent hospitalization for manic episode within the last 2 weeks.
4. History of seizure disorder or serious neurological condition (e.g., epilepsy, dementia,
traumatic brain injury).
5. Ongoing treatment with antipsychotics, antidepressants, or mood stabilizers that
cannot be safely discontinued (except lithium or valproate).
6. Use of CYP3A4 inducers/inhibitors or strong CNS-active agents (e.g., sedatives,
opioids, immunosuppressants) within the past 7 days.
7. Presence of uncontrolled medical illness, including:
o Cardiovascular disease with prolonged QTc
o Abnormal liver/renal function
o Severe endocrine disturbance
8. Current pregnancy, breastfeeding, or planning for major surgery during study
duration. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Change in MADRS score from baseline to the end of each 4-week treatment phase
(Lumateperone and OFC). |
weekly till 12 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| NIL |
NIL |
|
|
Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
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/ Phase 4 |
|
Date of First Enrollment (India)
|
11/04/2026 |
| 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="2"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| 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
|
Study OverviewThis research protocol outlines a 12-week, randomized, open-label, parallel-group clinical trial to compare the efficacy and safety of Lumateperone against the standard Olanzapine-Fluoxetine Combination (OFC) for treating bipolar depression. Background & RationaleWhile OFC is a proven, FDA-approved treatment for bipolar depression, it is heavily associated with adverse metabolic side effects, such as weight gain and metabolic syndrome. This is especially concerning in South Asian populations who are at a higher baseline risk for these issues. Lumateperone is a newer, FDA-approved atypical antipsychotic that shows similar promise for treating depressive symptoms but with a much safer metabolic profile. Currently, there are no head-to-head trials comparing the two, particularly in an Indian demographic. Key Methodological DetailsStudy Setting & Population: 30 adult patients (ages 18–65) with Bipolar I or II Disorder currently in a major depressive episode, recruited from AIIMS Bathinda.Intervention Arms: Arm A: Lumateperone (42 mg/day).Arm B: OFC (Olanzapine 5 mg + Fluoxetine 20 mg/day).Primary Endpoint: The mean change in depressive symptom severity from baseline to the end of the 12-week phase, measured by the Montgomery–Asberg Depression Rating Scale (MADRS).Secondary Endpoints: Response rates ($ge$ 50% MADRS reduction), remission rates (MADRS $le$ 10), and overall improvements in clinical status and quality of life (measured via CGI-S, CGI-I, and Q-LES-Q-SF).Analysis: Data will be analyzed using Intention-to-Treat (ITT) and Per-Protocol approaches in SPSS, assessing both symptom reduction and metabolic tolerability. |