APQ-TRD: Comparison of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment Resistant Depression

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04936126

Collaborator

Indian Council of Medical Research (Other)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The present study has been designed to compare the efficacy and safety of augmentation of SSRIs with Amantadine vs Pramipexole vs the recommended Quetiapine augmentation in Treatment-Resistant Depression (TRD) and correlate the changes in depression scores with changes in the serum levels of Brain-derived neurotrophic factor (BDNF) and Nerve growth factor (NGF).

The proposed study will be a prospective, randomized, single-blind, controlled clinical trial in patients with TRD and will be conducted over a period of 2 years. The study cohort will comprise 150 patients with unipolar depression clinically diagnosed as TRD, who are currently on Sertraline treatment (dose range = 100-200 mg/day). At baseline, Hamilton Depression Scale (HAM-D 21 item) will be administered to determine the severity of depressive symptoms, Clinical Global Inventory (CGI) will be administered to determine the baseline severity of the illness. Serum BDNF, and NGF will be estimated by ELISA using commercially available Human ELISA kit. The sample will be divided into 3 equal treatment groups by block randomization technique, each group comprising of 50 patients.

Group 1 will receive Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment. Group 2 will receive Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment. Group 3 will serve as the control arm and receive the recommended Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.

The study cohort will be reassessed for the changes in HAM-D scores, CGI severity scores, Improvement score and Efficacy index, at 4 and 8 weeks follow up. The changes in Serum BDNF, and NGF will be estimated at the end of 8 weeks, to correlate with the change in severity of depressive symptoms. All the participants will be evaluated for any untoward side effects in a prescribed format for the Pharmacovigilance program of India (PVPI). The patient in either of the treatment arms, who are not responding to treatment or relapsing with aggravation of depressive symptoms will be switched on to Venlafaxine treatment or Electro-convulsive therapy (ECT) as decided by the treating team.

Condition or Disease	Intervention/Treatment	Phase
Treatment Resistant Depression	Drug: Quetiapine Drug: Amantadine Drug: Pramipexole	Phase 4

Detailed Description

STUDY OBJECTIVES:

Primary Objective

• To compare the change in the severity of symptoms of depression in terms of change in HAM-D scores between the treatment groups over 8 weeks.

Secondary Objective

To compare the change in CGI scores between the treatment groups over 8 weeks.
To evaluate the change in serum BDNF, serum NGF levels between the treatment groups over 8 weeks.
To detect adverse drug reactions (if any) (prescribed format for Pharmacovigilance program of India PVPI)

Study design:

This study will be a hospital-based, prospective, randomized, single-blind, controlled clinical trial in patients with unipolar depression clinically diagnosed as TRD, which will be conducted over a period of 3 years.

Study population and eligibility:

The study cohort will comprise of 150 patients with the diagnosis of unipolar treatment-resistant depression (TRD), attending the in-patient or out-patient department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar. The patient should have received adequate trials of at least two antidepressants (one of which preferably should be an SSRI) at adequate dose and duration (> 6 weeks), with poor clinical response while on regular compliance. The patients fulfilling the criteria who are currently on Sertraline treatment (dose range = 100-200 mg/day), giving written informed consent will be recruited for the present study. The detailed history, relevant socio-demographic, and clinical data will be collected in a structured case record form (CRF).

Study Procedure and Data collection:

Baseline assessment:

At baseline, Hamilton Depression Scale (HAM-D 21 item) will be administered to determine the severity of depressive symptoms, Clinical Global Inventory (CGI) will be administered to determine the baseline severity of the illness. Serum BDNF, and NGF will be estimated by ELISA using commercially available Human ELISA kit.

Randomization:

The study cohort of 150 participants will be randomized into three treatment groups by block randomization technique (computer-generated) with 25 blocks, each block with 6 participants. The sample will be divided into 3 equal treatment groups, each group comprising of 50 patients.

Treatment Allocation:

Follow up assessment:

The study cohort will be reassessed for the changes in HAM-D scores, CGI severity scores, Improvement score, and Efficacy index, at 4 and 8 weeks follow up. The changes in Serum BDNF and NGF will be estimated at the end of 8 weeks, to correlate with the change in the severity of depressive symptoms.

Rescue Medication:

The patient in either of the treatment arms, who are not responding to treatment or relapsing with aggravation of depressive symptoms will be switched on to Venlafaxine treatment or ECT as decided by the treating team.

Safety evaluation:

All the participants will be evaluated for any untoward side effects like insomnia, restlessness, and agitation, etc. which will be documented and informed to the institutional ethics committee.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, parallel-arm, randomized, single-blind, controlled clinical trialProspective, parallel-arm, randomized, single-blind, controlled clinical trial

Masking:

Single (Outcomes Assessor)

Masking Description:

The outcome assessor will remain blind to the treatment allocation

Primary Purpose:

Treatment

Official Title:

Comparative Efficacy of Antidepressant Augmentation With Amantadine vs Pramipexole vs Quetiapine in Treatment-resistant Unipolar Depression: A Randomized Controlled Trial.

Anticipated Study Start Date :

Aug 7, 2021

Anticipated Primary Completion Date :

Jul 7, 2024

Anticipated Study Completion Date :

Sep 7, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Quetiapine group Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.	Drug: Quetiapine Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment for the study period
Experimental: Amantadine group Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment	Drug: Amantadine Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment for the study period
Experimental: Pramipexole group Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment	Drug: Pramipexole Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment for the study period

Arm

Intervention/Treatment

Active Comparator: Quetiapine group

Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment.

Drug: Quetiapine

Quetiapine XR 100 mg/day augmentation to the ongoing Sertraline treatment for the study period

Experimental: Amantadine group

Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment

Drug: Amantadine

Amantadine 200 mg/day (in two divided doses) augmentation to the ongoing Sertraline treatment for the study period

Experimental: Pramipexole group

Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment

Drug: Pramipexole

Pramipexole 0.375 mg/day (in three divided doses) augmentation to the ongoing Sertraline treatment for the study period

Outcome Measures

Primary Outcome Measures

Hamilton Depression Scale scores [8 weeks]
Change in Hamilton Depression Scale scores 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression Higher scores indicating higher severity of depression

Secondary Outcome Measures

Clinical Global Impression scores [8 weeks]
Change in Clinical Global Impression scores CGI-S severity scores range from 1-7, with higher scores indicating greater severity of illness CGI-I Improvement score range from 1-7, with lower scores indicating improvement and higher scores indicating worsening
Serum Brain Derived Neurotrophic Factor [8 weeks]
Change in Serum Brain Derived Neurotrophic Factor levels
Serum Nerve Growth Factor [8 week]
Change in Serum Nerve Growth Factor
Rescue Medications [8 weeks]
Number of patients in the Rescue medication group

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with unipolar depression clinically diagnosed as TRD, who are currently on Sertraline treatment (dose range = 100-200 mg/day)
Patients aged 18-60 years of either sex