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

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ClinicalTrials.gov Identifier: NCT03887624
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Xu Yi, Zhejiang University

Tracking Information
First Submitted Date  ICMJE March 2, 2019
First Posted Date  ICMJE March 25, 2019
Last Update Posted Date July 8, 2019
Actual Study Start Date  ICMJE May 21, 2019
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigate the Clinical Responses of Ethosuximide in Patients With Treatment-Resistant Depression.
Official Title  ICMJE 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.
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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
Condition  ICMJE Depressive Disorder, Treatment-Resistant
Intervention  ICMJE
  • 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: 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, 20mg/day, take it orally after breakfast, take it for 4 weeks without interruption.
    Other Name: Lexapro
Study Arms  ICMJE
  • Experimental: Experimental group
    Ethosuximide(2 weeks) + Escitalopram (4 weeks)
    Interventions:
    • Drug: Ethosuximide
    • Drug: Escitalopram
  • Placebo Comparator: Control group
    Placebo(2 weeks)+Escitalopram(4 weeks)
    Interventions:
    • Drug: Placebo
    • Drug: Escitalopram
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 20, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2020
Estimated Primary Completion Date April 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shaohua Hu, Doctor of Medicine 86-571-87232232 dorhushaohua@zju.edu.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03887624
Other Study ID Numbers  ICMJE 2019-716
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xu Yi, Zhejiang University
Study Sponsor  ICMJE Zhejiang University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yi Xu, Doctor of Medicine Department of psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine
PRS Account Zhejiang University
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP