Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT04847245
Recruitment Status : Not yet recruiting
First Posted : April 19, 2021
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Si Tianmei, Peking University

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.


Condition or disease Intervention/treatment Phase
Chronic Visceral Pain Major Depressive Disorder Drug: Pregabalin 75mg tid + Duloxetine Drug: Intravenous administration of esketamine 0.125 mg/kg+Duloxetine Drug: Intravenous administration of esketamine 0.25 mg/kg +Duloxetine Drug: Intravenous administration of esketamine 0.50 mg/kg+Duloxetine Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 1, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Pregabalin group
Pregabalin capsules were administered orally (75 mg, tid), combined administration of duloxetine.
Drug: Pregabalin 75mg tid + Duloxetine
Pregabalin capsules were administered orally (75 mg, 3 times a day), combined administration of duloxetine (60-120 mg/day).

Experimental: 0.125 mg/kg esketamine group
Intravenous administration of esketamine 0.125 mg/kg,and duloxetine is co- administered orally.
Drug: Intravenous administration of esketamine 0.125 mg/kg+Duloxetine
Intravenous administration of esketamine 0.125 mg/kg (2 times per week), combined oral administration of duloxetine (60-120 mg/day)

Experimental: 0.25 mg/kg esketamine group
Intravenous administration of esketamine 0.25mg/kg,and duloxetine is co- administered orally.
Drug: Intravenous administration of esketamine 0.25 mg/kg +Duloxetine
Intravenous administration of esketamine 0.25 mg/kg (2 times per week), combined oral administration of duloxetine (60-120 mg/day)

Experimental: 0.50 mg/kg esketamine group
Intravenous administration of esketamine 0.50 mg/kg,and duloxetine is co- administered orally.
Drug: Intravenous administration of esketamine 0.50 mg/kg+Duloxetine
Intravenous administration of esketamine 0.50 mg/kg (2 times per week), combined oral administration of duloxetine (60-120 mg/day)




Primary Outcome Measures :
  1. Visual Analogue Scale (VAS) [ Time Frame: Day 0 to Day 28 ]
    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 :
  1. Hamilton Depression Rating Scale (HAMD) [ Time Frame: Day 0 to Day 28 ]
    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.

  2. Short Form 12 Health Survey (SF-12) [ Time Frame: Day 0 to Day 28 ]
    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).

  3. Hamilton Anxiety Scale (HAMA) [ Time Frame: Day 0 to Day 28 ]
    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.

  4. Changes in serum inflammatory factors [ Time Frame: Day 0 to Day 28 ]
    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.

  5. Electroencephalogram (EEG) [ Time Frame: Day 0 to Day 28 ]
    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.

  6. Functional magnetic resonance imaging (fMRI) [ Time Frame: Day 0 to Day 28 ]
    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.



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 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. aged 18 to 55
  2. Those who can understand and obey the research plan
  3. Sign the informed consent form voluntarily
  4. Those who meet the DSM-IV-TR depression diagnostic criteria and have first or second episodes of depression
  5. Hamilton Depression Scale score ≥ 14 points
  6. 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.
  7. No systemic use of antidepressants and analgesics within 2 weeks after enrollment.

    -

Exclusion Criteria:

  1. Female patients who are pregnant, breastfeeding, or preparing to conceive
  2. Allergic to duloxetine or pregabalin in the past.
  3. A history of serious or unstable physical diseases, such as cardiovascular/liver/kidney/respiratory/ endocrine/nervous/ blood system disease.
  4. 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.);
  5. 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.).
  6. Patients with a history of adverse reactions to multiple drugs.
  7. The patient is taking psychotropic drugs, including benzodiazepines, sleeping pills, anticonvulsants, etc.
  8. 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)
  9. Received electroconvulsive therapy within 6 months before enrollment.
  10. Those who are currently at serious risk of suicide, and a score of 3 or higher in item 3 of the 17-HAMD .

    -


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): NCT04847245


Contacts
Layout table for location contacts
Contact: Tianmei SI, PhD., MD 86-1062723748 si.tian-mei@163.com
Contact: Yunai Su, PhD 86-10-62723767 suyunai@163.com

Sponsors and Collaborators
Peking University
Layout table for additonal information
Responsible Party: Si Tianmei, Professor, Peking University
ClinicalTrials.gov Identifier: NCT04847245    
Other Study ID Numbers: Esketamine20210221
First Posted: April 19, 2021    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021

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 Si Tianmei, Peking University:
Esketamine
Pregabalin
Efficacy and Safety
Chronic Visceral Pain
Major depressive disorder
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Visceral Pain
Depressive Disorder
Depression
Depressive Disorder, Major
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Nociceptive Pain
Pain
Neurologic Manifestations
Pregabalin
Duloxetine Hydrochloride
Esketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors