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

NCT04847245 | Unknown

• 1 other identifier: Esketamine20210221
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Visceral Pain; Major Depressive Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 0 to Day 28

Secondary Outcomes (6)

• Hamilton Depression Rating Scale (HAMD)

  Day 0 to Day 28

• Short Form 12 Health Survey (SF-12)

  Day 0 to Day 28

• Hamilton Anxiety Scale (HAMA)

  Day 0 to Day 28

• Changes in serum inflammatory factors

  Day 0 to Day 28

• Electroencephalogram (EEG)

  Day 0 to Day 28

Study Arms (4)

Pregabalin group

ACTIVE COMPARATOR

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

Drug: Pregabalin 75mg tid + Duloxetine

0.125 mg/kg esketamine group

EXPERIMENTAL

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

Drug: Intravenous administration of esketamine 0.125 mg/kg+Duloxetine

0.25 mg/kg esketamine group

EXPERIMENTAL

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

Drug: Intravenous administration of esketamine 0.25 mg/kg +Duloxetine

0.50 mg/kg esketamine group

EXPERIMENTAL

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

Drug: Intravenous administration of esketamine 0.50 mg/kg+Duloxetine

Interventions

Pregabalin 75mg tid + Duloxetine DRUG

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

Pregabalin group

Intravenous administration of esketamine 0.125 mg/kg+Duloxetine DRUG

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

0.125 mg/kg esketamine group

Intravenous administration of esketamine 0.25 mg/kg +Duloxetine DRUG

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

0.25 mg/kg esketamine group

Intravenous administration of esketamine 0.50 mg/kg+Duloxetine DRUG

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

0.50 mg/kg esketamine group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Peking University: lead

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Pregabalin; Duloxetine Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Thiophenes; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Tianmei SI, PhD., MD

CONTACT

86-1062723748; si.tian-mei@163.com

Yunai Su, PhD

CONTACT

86-10-62723767; suyunai@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 14, 2021
• First Posted: April 19, 2021
• Study Start: May 1, 2021
• Primary Completion: December 31, 2022
• Study Completion: March 1, 2023
• Last Updated: April 19, 2021

Record last verified: 2021-04