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Esketamine Adjuvant Therapy for Patients With Chronic Visceral Pain Comorbid Major Depressive Disorder

Primary Purpose

Chronic Visceral Pain, Major Depressive Disorder

Status

Unknown status

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Pregabalin 75mg tid + Duloxetine

Intravenous administration of esketamine 0.125 mg/kg+Duloxetine

Intravenous administration of esketamine 0.25 mg/kg +Duloxetine

Intravenous administration of esketamine 0.50 mg/kg+Duloxetine

About this trial

This is an interventional treatment trial for Chronic Visceral Pain focused on measuring Esketamine, Pregabalin, Efficacy and Safety, Chronic Visceral Pain, Major depressive disorder

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

aged 18 to 55
Those who can understand and obey the research plan
Sign the informed consent form voluntarily
Those who meet the DSM-IV-TR depression diagnostic criteria and have first or second episodes of depression
Hamilton Depression Scale score ≥ 14 points
Those who meet the ICD-11 pain diagnostic criteria, and visual analogue scale score ≥ 7 points. Those who have chronic visceral pain instead of cancer pain.
No systemic use of antidepressants and analgesics within 2 weeks after enrollment.
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Exclusion Criteria:

Female patients who are pregnant, breastfeeding, or preparing to conceive
Allergic to duloxetine or pregabalin in the past.
A history of serious or unstable physical diseases, such as cardiovascular/liver/kidney/respiratory/ endocrine/nervous/ blood system disease.
A history of epileptic seizures or brain injury, or any neurological disease (including multiple sclerosis, degenerative diseases such as acute lateral sclerosis, Parkinson's disease and movement disorders, etc.);
In the last 12 months, the patient has the following medical history or its main diagnosis (DSM-IV-TR) is organic mental disorder, schizophrenia, schizoaffective mental disorder, delusional mental disorder, indeterminate mental disorder, Bipolar disorder, psychotic characteristics that are coordinated or uncoordinated with the mood, and history of substance abuse (including alcohol, psychoactive substances, etc.).
Patients with a history of adverse reactions to multiple drugs.
The patient is taking psychotropic drugs, including benzodiazepines, sleeping pills, anticonvulsants, etc.
During the depressive episode, treatment with at least 2 antidepressants in a sufficient course of treatment or at least one SSRI antidepressant treatment is ineffective. A sufficient dose of treatment means treatment with fluoxetine ≥40 mg/day (or sertraline ≥100 mg/day, paroxetine> 40 mg/day, fluvoxamine> 100 mg/day, citalopram> 40 mg /Day, escitalopram> 20 mg/day, venlafaxine> 150 mg/day, duloxetine> 80 mg/day)
Received electroconvulsive therapy within 6 months before enrollment.
Those who are currently at serious risk of suicide, and a score of 3 or higher in item 3 of the 17-HAMD .
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Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Pregabalin group

0.125 mg/kg esketamine group

0.25 mg/kg esketamine group

0.50 mg/kg esketamine group

Arm Description

Pregabalin capsules were administered orally (75 mg, tid), combined administration of duloxetine.

Intravenous administration of esketamine 0.125 mg/kg，and duloxetine is co- administered orally.

Intravenous administration of esketamine 0.25mg/kg，and duloxetine is co- administered orally.

Intravenous administration of esketamine 0.50 mg/kg，and duloxetine is co- administered orally.

Outcomes

Primary Outcome Measures

Visual Analogue Scale (VAS)

The pain VAS is a unidimensional measure of pain intensity, which has been widely used in diverse adult populations, including those with chronic visceral pain. The minimus value is 0 and the maximum value is 10. Higher scores mean a worse outcome.

Secondary Outcome Measures

Hamilton Depression Rating Scale (HAMD)

The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The minimum value is 0 and the maximum value is 52. Higher scores mean a worse outcome.

Short Form 12 Health Survey (SF-12)

SF-12 is a 12-item, patient-reported survey of patient health, and is widely used since it produces similar results for physical and mental health scores with far less respondent burden for producing scores of overall mental and physical well-being. The SF-12 yields an eight-scale profile of scores as well as physical and mental health summary measures. Answers to questions of these subscales are combined (weighted) with Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) scale scores. SF-12 scales and summary measures are scored so that a higher score indicates a better health state. After recoding raw scores for some items (BP, GH, VT, and one item from MH), the raw scores could be transformed to provide scores for eight scales, each ranging from 0 (the worst) to 100 (the best).

Hamilton Anxiety Scale (HAMA)

The HAMA is a psychological questionnaire used by clinicians to rate the severity of a patient's anxiety. The scale consists of 14 items designed to assess the severity of a patient's anxiety. Each of the 14 items contains a number of symptoms, and each group of symptoms is rated on a scale of zero to four, with four being the most severe. The minimum value is 0 and the maximum value is 56. Higher scores mean a worse outcome.

Changes in serum inflammatory factors

Explore the action mechanism of esketamine on patients with chronic visceral pain comorbid depression from the level of blood inflammatory factors, including cytokines IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, etc.

Electroencephalogram (EEG)

Calculate the time-frequency characteristics of EEG data in each frequency band (delta wave, <4 Hz; theta wave, 4-8 Hz; alpha wave, 8-12 Hz and beta wave, 12-30 Hz) during the study period.

Functional magnetic resonance imaging (fMRI)

The regional brain activity, including fractional amplitude of low frequency fluctuation (fALFF) and regional homogeneity (ReHo) values, will be computed and assessed. In addtion, the large-scale brain networks and edge-wise connections in patients will be explored based on the theory of brain networks during the study period.

Full Information

NCT ID

NCT04847245

First Posted

March 14, 2021

Last Updated

April 14, 2021

Sponsor

Peking University

1. Study Identification

Unique Protocol Identification Number

NCT04847245

Brief Title

Esketamine Adjuvant Therapy for Patients With Chronic Visceral Pain Comorbid Major Depressive Disorder

Official Title

A Randomized Controlled, Single-blind, Esketamine Adjuvant Therapy for the Efficacy and Safety of Patients With Chronic Visceral Pain Comorbid Major Depressive Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

May 1, 2021 (Anticipated)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

March 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Ketamine is a dissociative anesthetic and powerful analgesic. At low doses, ketamine can desensitize the central pain pathway and modulate opioid receptors. Studies have generally found that preoperative use of ketamine can reduce opioid consumption by approximately 50% and sub-anaesthetic doses of it have a rapid antidepressant effect, especially refractory depression. Studies have confirmed that esketamine, the S(+) enantiomer of ketamine, has a stronger affinity for NMDA receptors, which can achieve the same effect at smaller doses. While the incidence of neuropsychiatric side effects is significantly lower. On March 4, 2019, the U.S. Food and Drug Administration (FDA) first approved esketamine nasal spray with a new mechanism of action for the treatment of adult patients with refractory depression. Based on the analgesic and antidepressant effects of ketamine, the investigators speculate that esketamine may be effective for patients with chronic visceral pain comorbid depression. At present, the research evidence in this area is relatively lacking. Therefore, this study aims to explore the difference in the efficacy and safety of esketamine as an adjuvant therapy and positive control drug-pregabalin in patients with chronic visceral pain comorbid depression. Detailed Description: According to the inclusion criteria and exclusion criteria, select patients with chronic visceral pain comorbid depression. Filtering and grouping period: During this phase, the patient will sign an informed consent form, and then conduct a structured clinical evaluation to determine whether it meets the "depressive disorder" in the DSM-IV-TR diagnostic criteria. According to the ICD-11, determine whether the patients have chronic visceral pain. Acute treatment period: Randomize patients into the following treatment groups: intravenous administration of esketamine (3 groups, 0.125, 0.25, 0.50 mg/kg)， and duloxetine is co- administered orally. Pregabalin capsules were administered combined with duloxetine orally. observation period: After 2 weeks, esketamine treatment was discontinued, and observation was continued for 2 weeks. Maintain duloxetine and pregabalin treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Visceral Pain, Major Depressive Disorder

Keywords

Esketamine, Pregabalin, Efficacy and Safety, Chronic Visceral Pain, Major depressive disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pregabalin group

Arm Type

Active Comparator

Arm Description

Pregabalin capsules were administered orally (75 mg, tid), combined administration of duloxetine.

Arm Title

0.125 mg/kg esketamine group

Arm Type

Experimental

Arm Description

Intravenous administration of esketamine 0.125 mg/kg，and duloxetine is co- administered orally.

Arm Title

0.25 mg/kg esketamine group

Arm Type

Experimental

Arm Description

Intravenous administration of esketamine 0.25mg/kg，and duloxetine is co- administered orally.

Arm Title

0.50 mg/kg esketamine group

Arm Type

Experimental

Arm Description

Intravenous administration of esketamine 0.50 mg/kg，and duloxetine is co- administered orally.

Intervention Type

Drug

Intervention Name(s)

Pregabalin 75mg tid + Duloxetine

Intervention Description

Pregabalin capsules were administered orally (75 mg, 3 times a day), combined administration of duloxetine (60-120 mg/day）.

Intervention Type

Drug

Intervention Name(s)

Intravenous administration of esketamine 0.125 mg/kg+Duloxetine

Intervention Description

Intravenous administration of esketamine 0.125 mg/kg （2 times per week)， combined oral administration of duloxetine (60-120 mg/day）

Intervention Type

Drug

Intervention Name(s)

Intravenous administration of esketamine 0.25 mg/kg +Duloxetine

Intervention Description

Intravenous administration of esketamine 0.25 mg/kg （2 times per week)， combined oral administration of duloxetine (60-120 mg/day）

Intervention Type

Drug

Intervention Name(s)

Intravenous administration of esketamine 0.50 mg/kg+Duloxetine

Intervention Description

Intravenous administration of esketamine 0.50 mg/kg （2 times per week)， combined oral administration of duloxetine (60-120 mg/day）

Primary Outcome Measure Information:

Title

Visual Analogue Scale (VAS)

Description

Time Frame

Day 0 to Day 28

Secondary Outcome Measure Information:

Title

Hamilton Depression Rating Scale (HAMD)

Description

Time Frame

Day 0 to Day 28

Title

Short Form 12 Health Survey (SF-12)

Description

Time Frame

Day 0 to Day 28

Title

Hamilton Anxiety Scale (HAMA)

Description

Time Frame

Day 0 to Day 28

Title

Changes in serum inflammatory factors

Description

Time Frame

Day 0 to Day 28

Title

Electroencephalogram (EEG)

Description

Calculate the time-frequency characteristics of EEG data in each frequency band (delta wave, <4 Hz; theta wave, 4-8 Hz; alpha wave, 8-12 Hz and beta wave, 12-30 Hz) during the study period.

Time Frame

Day 0 to Day 28

Title

Functional magnetic resonance imaging (fMRI)

Description

Time Frame

Day 0 to Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: aged 18 to 55 Those who can understand and obey the research plan Sign the informed consent form voluntarily Those who meet the DSM-IV-TR depression diagnostic criteria and have first or second episodes of depression Hamilton Depression Scale score ≥ 14 points Those who meet the ICD-11 pain diagnostic criteria, and visual analogue scale score ≥ 7 points. Those who have chronic visceral pain instead of cancer pain. No systemic use of antidepressants and analgesics within 2 weeks after enrollment. - Exclusion Criteria: Female patients who are pregnant, breastfeeding, or preparing to conceive Allergic to duloxetine or pregabalin in the past. A history of serious or unstable physical diseases, such as cardiovascular/liver/kidney/respiratory/ endocrine/nervous/ blood system disease. A history of epileptic seizures or brain injury, or any neurological disease (including multiple sclerosis, degenerative diseases such as acute lateral sclerosis, Parkinson's disease and movement disorders, etc.); In the last 12 months, the patient has the following medical history or its main diagnosis (DSM-IV-TR) is organic mental disorder, schizophrenia, schizoaffective mental disorder, delusional mental disorder, indeterminate mental disorder, Bipolar disorder, psychotic characteristics that are coordinated or uncoordinated with the mood, and history of substance abuse (including alcohol, psychoactive substances, etc.). Patients with a history of adverse reactions to multiple drugs. The patient is taking psychotropic drugs, including benzodiazepines, sleeping pills, anticonvulsants, etc. During the depressive episode, treatment with at least 2 antidepressants in a sufficient course of treatment or at least one SSRI antidepressant treatment is ineffective. A sufficient dose of treatment means treatment with fluoxetine ≥40 mg/day (or sertraline ≥100 mg/day, paroxetine> 40 mg/day, fluvoxamine> 100 mg/day, citalopram> 40 mg /Day, escitalopram> 20 mg/day, venlafaxine> 150 mg/day, duloxetine> 80 mg/day) Received electroconvulsive therapy within 6 months before enrollment. Those who are currently at serious risk of suicide, and a score of 3 or higher in item 3 of the 17-HAMD . -

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tianmei SI, PhD., MD

Phone

86-1062723748

si.tian-mei@163.com

First Name & Middle Initial & Last Name or Official Title & Degree

Yunai Su, PhD

Phone

86-10-62723767

suyunai@163.com

12. IPD Sharing Statement

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Esketamine Adjuvant Therapy for Patients With Chronic Visceral Pain Comorbid Major Depressive Disorder

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