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Antidepressant Effects of TS-161 in Treatment-Resistant Depression

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ClinicalTrials.gov Identifier: NCT04821271
Recruitment Status : Recruiting
First Posted : March 29, 2021
Last Update Posted : February 3, 2023
Sponsor:
Collaborator:
Taisho Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Study Description
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Brief Summary:

Background:

Major depressive disorder (MDD) is a common, chronic mental illness. It can take weeks to months for antidepressants to work. Researchers want to test a new drug that might act more rapidly.

Objective:

To see if TS-161 will improve symptoms of depression in people with MDD.

Eligibility:

Adults ages 18-65 with MDD without psychotic features.

Design:

Participants will be screened under a separate protocol. They will have blood tests. They will complete surveys about their symptoms.

Participants will have an inpatient visit at NIH. Participation may last 12-16 weeks.

During the first phase of the study, participants will be tapered off their psychiatric medicines. For 2 weeks they will have a drug-free period.

During Phase II participants will take TS-161 or placebo. They will take TS-161 for 3 weeks and placebo for 3 weeks. In between the 3-week time period, they will have 2-3 weeks where they will be drug free. Participants will also have the following tests during this time:

  • Interviews
  • Physical exams
  • Psychological tests and surveys about their symptoms
  • Blood draws and urine samples
  • They may complete tests of mood and thinking
  • MRI (Magnetic resonance imaging): Participants will lie in a machine that takes pictures of their brain.
  • Functional MRIs: They will perform tasks displayed on a computer screen inside the MRI scanner
  • MEG (magnetoencephalography): Participants will lie down and do tasks of memory, attention, and thinking. A cone lowered on their head will record brain activity.
  • Electrocardiograms to record the heart s electrical activity. Electrodes will be placed on the skin....

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Treatment-Resistant Depression Depression Other: Placebo Drug: TS-161 (50 - 100 mg) Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Investigation of the Antidepressant Effects of the mGlu2/3 Receptor Antagonist TS-161 in Treatment-Resistant Depression
Actual Study Start Date : June 10, 2021
Estimated Primary Completion Date : June 3, 2023
Estimated Study Completion Date : June 3, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arms and Interventions
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Arm Intervention/treatment
Experimental: 1
Individuals in Arm 1 will receive daily double-blinded TS-161 for three weeks during Test Session 1 and daily double-blinded placebo for three weeks during Test Session 2.
 Other: Placebo
Arm 1 and 2 Control Intervention

Drug: TS-161 (50 - 100 mg)
Arm 1 and 2 Experimental Intervention
Experimental: 2
Individuals in Arm 2 will receive daily double-blinded placebo for three weeks during Test Session 1 and daily double-blinded TS-161 for three weeks during Test Session 2.
 Other: Placebo
Arm 1 and 2 Control Intervention

Drug: TS-161 (50 - 100 mg)
Arm 1 and 2 Experimental Intervention


Outcome Measures
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Primary Outcome Measures :
  1. Change from baseline on Montgomery-Asberg Depression Rating Scale (MADRS) total scores [ Time Frame: Baseline, Day 21 ]
    Clinical rating scale of depression


Secondary Outcome Measures :
  1. Proportion of participants in remission (defined as MADRS total score =10) [ Time Frame: Baseline, 230 min post-drug, and Days 1, 2, 3, 7, 14, and 21, per Test Session. ]
    Clinical rating scale of depression

  2. Proportion of participants achieving response (defined as a >/=50% reduction from baseline in MADRS total score). [ Time Frame: Baseline, 230 min post-drug, and Days 1, 2, 3, 7, 14, and 21, per Test Session. ]
    Clinical rating scale of depression

  3. Incidence of AEs and total scores using the Clinician Administered Dissociative States Scale (CADSS), Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale (BPRS), vital signs, changes in clinical laboratory evaluations, and ECGs. [ Time Frame: At specific timepoints within each treatment condition indicated in the protocol. ]
    Measures and evaluations assess various aspects of clinical condition, adverse events, and mood and anxiety symptomology

  4. Gamma power measured via MEG [ Time Frame: Baseline, 120 min post-dose, Day 21 ]
    Measurement of glutamate and glutamine levels

  5. Changes in activity in the frontolimbic circuitry [ Time Frame: Baseline, 240 min post-dose, Day 21 ]
    fMRI is used to measure frontolimbic circuitry

  6. Change from baseline on the HDRS, HAM-A, the PANAS, Snaith Hamilton Pleasure Scale (SHAPS), and the Temporal Experience of Pleasure Scale (TEPS) scales. [ Time Frame: Baseline, 230 min post-drug, and Days 1, 2, 3, 7, 14, and 21, per Test Session. ]
    Clinical rating scales of mood, anxiety, and anhedonia.

  7. Change from baseline on MADRS total scores [ Time Frame: Baseline, 230 min post-drug, and Days 1, 2, 3, 7, and 14, per Test Session. ]
    Clinical rating scale of depression

  8. Change from baseline on item 10 (suicidality) of the MADRS and total score on the C-SSRS, and the Scale for Suicidal Ideation (SSI). [ Time Frame: Baseline, 230 min post-drug, and Days 1, 2, 3, 7, 14, and 21, per Test Session. ]
    Clinical assessments of suicidality

  9. [1]H-MRS correlates with changes in MADRS score [ Time Frame: Baseline, 240 min post-drug, Day 21, per Test Session ]
    MADRS: Clinical rating scale of depression; MRS: Measurement of glutamate and glutamine levels


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Participants may be eligible for this study if they:

  1. Are able to understand the study and can provide your own consent.
  2. Are willing to undergo all study procedures and are available for the duration of the study.
  3. Are aged 18 to 65.
  4. Have major depressive disorder.
  5. Have a current episode of depression lasting at least 4 weeks.
  6. Ability to take oral medication.
  7. Have not responded to at least one antidepressant.
  8. For females of reproductive potential: use of contraception while in the study and for an additional 4 weeks after stopping the study drug.
  9. For males of reproductive potential: use of condoms or other types of birth control with partner while in the study and for an additional 3 months after stopping the study drug.
  10. Agree to be hospitalized at the NIH Clinical Center.
  11. Abstain from alcohol and drug use while in the study.

EXCLUSION CRITERIA:

Participants may not be eligible for this study if they:

  1. Are taking any medications that might make it unsafe for you to receive TS-161 or might interfere with our study results.
  2. Have been treated with a reversible monoamine oxidase inhibitor (such as phenelzine (Nardil) and tranylcypromine (Parnate)), clozapine, or electroconvulsive therapy (ECT) less than 4 weeks before Phase II.
  3. Have been treated with fluoxetine, aripiprazole, or brexpiprazole less than 5 weeks before Phase II.
  4. Have ever undergone deep brain stimulation.
  5. Have taken ketamine or esketamine for the treatment of depression but did not respond.
  6. Are unwilling to stop undergoing one-on-one psychotherapy for the duration of the study.
  7. Are pregnant or plan to become pregnant in the next 12 to 16 weeks while in the study, or are breast-feeding.
  8. Have schizophrenia or any other psychotic disorder.
  9. Had significant drug or alcohol dependence or abuse in the past 3 months (except for nicotine or caffeine), or are currently using illicit substances.
  10. Have been diagnosed with borderline or antisocial personality disorder.
  11. Had a head injury that caused a loss of consciousness for more than 5 minutes (for the brain imaging).
  12. Have a medical illness that might make your participation unsafe, such as heart (including coronary artery disease, atherosclerotic ischemic stroke, and atrial fibrillation), liver, respiratory, blood, immune, or kidney disease or a seizure disorder, based on our evaluation.
  13. Have abnormal results on blood and urine tests we will do.
  14. Have significant suicidal or homicidal thoughts.
  15. Have a positive HIV test.
  16. For brain imaging: Have metal in your body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if you were a welder or metal worker, since you may have small metal fragments in the eye.
  17. Weigh over 245 lbs and cannot fit into the MRI scanner.
  18. Have a positive, or suspected positive, COVID-19 test.
  19. Are an NIMH staff member or an immediate family member of an NIMH staff member.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04821271


Contacts
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Contact: Carlos A Zarate, M.D. (877) 646-3644 moodresearch@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Taisho Pharmaceutical Co., Ltd.
Investigators
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Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
More Information
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Additional Information:

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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT04821271    
Other Study ID Numbers: 10000101
000101-M
First Posted: March 29, 2021    Key Record Dates
Last Update Posted: February 3, 2023
Last Verified: February 1, 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .Clinical and demographic and biomarker participant data collected during the trial, after deidentification.
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: Starting within 1 year of completion of the study.
Access Criteria: Branch Chief will review requests and access will need to be approved by the NIMH/DIRP SD and OCD NIMH and the NIH IRB.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Biomarker
Neurobiology
Glutamate
Magnetoencephalography
Magnetic Resonance Spectroscopy
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
 Behavioral Symptoms
Mood Disorders
Mental Disorders