Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Investigate the Clinical Responses of Ethosuximide in Patients With Treatment-Resistant Depression.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03887624
Recruitment Status : Not yet recruiting
First Posted : March 25, 2019
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Xu Yi, Zhejiang University

Brief Summary:
This study evaluates the efficacy and safety of ethosuximide in the treatment of refractory depressive disorder in adults. Half of participants will receive ethosuximide and escitalopram in combination, while the other half will receive a placebo and escitalopram.

Condition or disease Intervention/treatment Phase
Depressive Disorder, Treatment-Resistant Drug: Ethosuximide Drug: Placebo Drug: Escitalopram Early Phase 1

Detailed Description:
Ethosuximide is a inhibitor of low-voltage-sensitive T-type calcium channels(T-VSCCs). It has higher selectivity to T-VSCCs and can enter cerebrospinal fluid through the blood-brain barrier, inhibit T-VSCCs on the lateral habenular nucleus neurons, and then inhibit the cluster discharge of neurons, resulting in a rapid antidepressant effect.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

This study is a double-blind and double-simulation design. In the course of clinical study, all subjects, researchers and evaluators are blind to grouping information. The results of the study are audited by blind state data. The placebos are administered in capsules with no difference in appearance, color, weight or odor from the positive drugs. Both subjects and drugs are coded blindly.

In the study, the coding system for research drugs have an emergency blindness detection procedure, so as to quickly identify the drugs in emergency medical condition, without destroying the blind design of clinical research.

Primary Purpose: Treatment
Official Title: A Randomized, Parallel-group,Placebo-controlled, Double-blind Clinical Trial to Evaluate the Efficacy and Safety of Ethosuximide in Chinese Patients With Treatment-Resistant Depression.
Estimated Study Start Date : April 15, 2019
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : October 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental group
Ethosuximide(2 weeks) + Escitalopram (4 weeks)
Drug: Ethosuximide
2 times/day, take it orally after breakfast/dinner; take 500mg in the morning and 500mg in the evening on day1, 500mg in the morning and 750mg in the evening on day2, 750mg in the morning and 750mg in the evening on day3, 750mg in the morning and 1000mg in the evening on day4, 1000mg in the morning and 1000mg in the evening on day5, maintain this dose until the end of treatment for 2 weeks.
Other Name: Zarontin

Drug: Escitalopram
1 time/day, 10mg/day, take it orally after breakfast, take it for 4 weeks without interruption.
Other Name: Lexapro

Placebo Comparator: Control group
Placebo(2 weeks)+Escitalopram(4 weeks)
Drug: Placebo
2 times/day, take it orally after breakfast/dinner; take 500mg in the morning and 500mg in the evening on day1, 500mg in the morning and 750mg in the evening on day2, 750mg in the morning and 750mg in the evening on day3, 750mg in the morning and 1000mg in the evening on day4, 1000mg in the morning and 1000mg in the evening on day5, maintain this dose until the end of treatment for 2 weeks.
Other Name: Placebo(for Ethosuximide)

Drug: Escitalopram
1 time/day, 10mg/day, take it orally after breakfast, take it for 4 weeks without interruption.
Other Name: Lexapro




Primary Outcome Measures :
  1. Montgomery and Asberg Depression Rating Scale(MADRS) score [ Time Frame: baseline and 43 days ]

    The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal/symptom absent, 7 to 19 - mild depression, 20 to 34 - moderate depression, >34 - severe depression.

    Changes of MADRS score at therapeutic visit point compare with baseline.



Secondary Outcome Measures :
  1. Quick Inventory of Depressive Symptomatology-Self Report(QIDS-SR) score [ Time Frame: baseline and 43 days ]

    The QIDS-SR is a psychological questionnaire used by clinicians to measure 16 factors across 9 different criterion domains for major depression. It is scored by summing the highest response in each of a set of questions relating to sleep, weight and psychomotor symptoms and then adding the remaining items. Scores range from 0 to 27 which may then be categorised as indicating none [0-5], mild [6-10], moderate [11-15], severe [16-20] and very severe [21-27] depressive symptoms.

    Changes of QIDS-SR score at therapeutic visit point compare with baseline.


  2. Hamilton Anxiety Rating Scale(HAMA) score [ Time Frame: baseline and 43 days ]

    The HAMA is a psychological questionnaire used by clinicians to rate the severity of a patient's anxiety. Scores range from 0 to 56. A score of 17 or less indicates mild anxiety severity. A score from 18 to 24 indicates mild to moderate anxiety severity. Lastly, a score of 25 to 30 indicates a moderate to severe anxiety severity.

    Changes of HAMA score at therapeutic visit point compare with baseline.


  3. MADRS score [ Time Frame: baseline and 43 days ]

    Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6.

    Changes of individual score of MADRS at therapeutic visit point compare with baseline.


  4. Young manic rating scale(YMRS) score [ Time Frame: baseline and 43 days ]

    The Young Mania Rating Scale (YMRS) is an eleven-item multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes in children and young adults. The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms. Extremely high scores increase the risk of the child having bipolar disorder by a factor of 9, while extremely low scores decrease the risk by a factor of 10. A score of 13 or higher indicates a potential case of mania or hypomania, while a score of 21 or above indicates a probable case. The average score for children with mania is 25, while the average score for children with hypomania is 20.

    Changes of YMRS score at therapeutic visit point compare with baseline.


  5. Efficiency after 2 and 4 weeks of treatment. [ Time Frame: baseline, week 2 and week 4 ]
    Efficiency means that the score of MADRS decreases by more than or equal to 50% compared with its baseline score.

  6. Remission rate after 2 and 4 weeks of treatment. [ Time Frame: baseline, week 2 and week 4 ]
    Remission means that the total score of MADRS is less than 10.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Inpatient of both sexes are aged from 18 to 65 years;
  2. Diagnosis of major depressive disorder(single or recurrent episodes) is made according to DSM-V(the fifth Edition of Diagnostic and Statistical Manual of Mental Disorders) criteria;
  3. Subjects with previous or current depressive episodes did not response to two different antidepressants with recommended doses and adequate duration (maximum treatment dose of at least 6 weeks);
  4. The subjects who will score more than or equal to 22 points on the MADRS scale at screening and baseline period;
  5. The subjects who will score more than or equal to 3 points on the first clause of MADRS scale at screening and baseline period;
  6. Subjects who will sign written informed consent and volunteer to participate in the clinical study.

Exclusion criteria

  1. Diagnoses of other mental disorders (such as organic mental disorders, schizophrenia, bipolar and related disorders, anxiety disorders, obsessive-compulsive disorders and so on) are made according to DSM-V criteria;
  2. Depressive episodes, such as depression caused by hypothyroidism, secondary to a systemic disease or an organic mental disorder caused by a neurological disease;
  3. Subjects with a history of attempted suicide, or currently at high suicide risk, or with suicide behavior/attempt, or scoring more than or equal to 3 points on the 10th clause of MADRS scale;
  4. Subject whose score of MADRS scale in baseline period will be 25% lower than that in screening period;
  5. Subjects with a history of severe or poorly controlled cardiovascular, liver, kidney, blood, endocrine, respiratory diseases, etc;
  6. Subjects with a history of epileptic seizures, except for a single febrile convulsion in children;
  7. Researchers believe that the results of subjects' physical and laboratory examinations are clinically significant abnormalities in screening or baseline period. The following indicators exceed the following criteria: 1)ALT or AST levels are 1.5 times higher than the upper limit of laboratory normal values. 2)Thyroid Function are 1.1 times higher than the upper or lower limit of normal values. 3) Serum creatinine values are 1.1 times higher than the upper limit of normal values. 4)The levels of blood urea nitrogen are higher than the upper limit of normal values;
  8. The result of electrocardiogram (ECG) is abnormal in screening or baseline period, such as male subjects with QTc interval (> 450 ms) and female subjects with QTc interval (> 470 ms) , and the researchers thought it is not suitable for selection;
  9. Subjects could not swallow oral medicines or have a history of gastrointestinal surgery or any other diseases that may interfere with drug absorption, distribution, metabolism or excretion;
  10. Monoamine oxidase inhibitors (MAOIs) are taken by subjects now or within 2 weeks before screening. Subjects who took antipsychotics, antidepressants or mood stabilizers before randomization and these drugs' cleaning phase had less than five half-lives. Subjects who took fluoxetine within 1 month before screening. Subjects who continue to take Chinese medicines with antidepressant effects specified in the instructions after signing informed consent.
  11. Subjects who received modified electroconvulsive therapy (MECT) , transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS), or systematic psychotherapy within 3 months before screening;
  12. Subjects with a history of allergies to two or more foods or drugs;
  13. Subjects who addicted to alcohol or substances within 6 months before screening;
  14. Prenatal, lactating, or reproductive women who had positive results of HCG tests before participating in the study; Male and female subjects will not take effective contraceptive measures or plan to be pregnant within 3 months after the study;
  15. Subjects who participated in clinical research within 30 days before signing the informed consent form for this study;
  16. According to the judgement of the researchers, other situations are not suitable for clinical research.

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): NCT03887624


Contacts
Layout table for location contacts
Contact: Shaohua Hu, Doctor of Medicine 86-571-87232232 dorhushaohua@zju.edu.cn

Locations
Layout table for location information
China, Zhejiang
Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine Not yet recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Shaohua Hu, Doctor of Medicine    86-571-87232232    dorhushaohua@zju.edu.cn   
Sponsors and Collaborators
Zhejiang University
Investigators
Layout table for investigator information
Principal Investigator: Yi Xu, Doctor of Medicine Department of psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine
  Study Documents (Full-Text)

Documents provided by Xu Yi, Zhejiang University:
Study Protocol  [PDF] March 11, 2019
Statistical Analysis Plan  [PDF] March 11, 2019
Informed Consent Form  [PDF] March 11, 2019


Publications:
Layout table for additonal information
Responsible Party: Xu Yi, Doctor of Medicine, Zhejiang University
ClinicalTrials.gov Identifier: NCT03887624     History of Changes
Other Study ID Numbers: 2018-972
First Posted: March 25, 2019    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xu Yi, Zhejiang University:
Depressive Disorder, Treatment-Resistant
ethosuximide

Additional relevant MeSH terms:
Layout table for MeSH terms
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Citalopram
Dexetimide
Ethosuximide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Anticonvulsants