Neurochemical, Metabonomics and Neuroimaging Characterization of TCM Diagnostic Subtypes of Major Depression Disorder (NMNTDM)

Neurochemical,Metabonomics and Neuroimaging Characterization of TCM Diagnostic Subtypes of Major Depression Disorder

There is heterogeneity in patients with depression. Many scholars propose that individualization of antidepressant achieves better outcomes. However, the scientific theoretical basis of individualized treatment is still quite weak. Different clinical subtypes of depression and their possible biomarkers are critically needed to provide the individualization with theoretical base. Diagnostic types of major depression disorder (MDD) based on the Theory of Traditional Chinese Medicine (TCM) and possible differentiations in neurobiochemistry, metabonomics and neuroimaging could be one of ways to explore the biomarkers and support the theory of the individualized treatment.

The hypothesized results will be of help to clarify the biological basis of MDD with LDQS and with DBHS, to provide the TCM with further scientific evidence, to explore the pathogenesis of depression, to improve the objective diagnosis of depression, and to promote targeted interventions by Western medicine, TCM or both.

Study Overview

• Status: Unknown
• Conditions: Severe Major Depression Disorder
• Intervention / Treatment: Drug: venlafaxine

Detailed Description

The objectives of this study is to explore if there are any differences in neurobiochemistry, metabonomics and neuroimaging (1) at the baseline, between the subjects who are the normal controls (C Group) and who both meet diagnostic criteria of the Diagnostic and Statistical Manual of 5th edition (DSM-V) on MDD and TCM criteria of 'pattern of Liver Depression and Qi Stagnation (LDQS)' or'pattern of Deficiency of Both Heart and Spleen (DBHS)' (T Group); (2) at the baseline, between the MDD subjects of LDQS and DBHS; (3) after 6-week venlafaxine administration, between the MDD subjects of LDQS and DBHS. 50 subjects in T Group and 25 in C Group are recruited in the study and the main laboratory tests include High Performance Liquid Chromatography(HPLC), Gas Chromatography-Mass Spectrum(GCMS) and neuroimaging DTI technology.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310012
      • Recruiting
      • Tongde Hospital of Zhejiang Province
      • Contact: Feng Bin, bachelor; Phone Number: +860571 89972003; Email: fengbintd@aliyun.com
      • Contact: Zhang jianmin, Ph.d; Phone Number: +86057189972008; Email: jianmin.3.zhang@kcl.ac.uk
      • Principal Investigator: Zhang-jin Zhang, Professor
      • Principal Investigator: Bin Feng, Professor
      • Sub-Investigator: Jiong Chen, physician
      • Sub-Investigator: ya-ping Li, Professor
      • Principal Investigator: Jin-bao Pu, researcher
      • Sub-Investigator: Wei-qing Liang, researcher
      • Sub-Investigator: Hong-xia Zhang, Radiologist
      • Sub-Investigator: Wen-song Chen, physician
      • Sub-Investigator: Zheng-xin Chen, physician
      • Sub-Investigator: Cheng-yu Gu, physician
      • Sub-Investigator: Pei-rong Wang, physician
      • Sub-Investigator: Yong-chun Ma, physician
      • Sub-Investigator: Yin Zhang, physician
      • Sub-Investigator: Chun-yu Yang, physician
      • Sub-Investigator: Bao-ping Xing, physician
      • Sub-Investigator: Wei-dong Jin, physician
      • Sub-Investigator: Yuan-Yuan Zhang, physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Had a diagnosis of major depressive disorder according to DSM-V and TCM criteria of 'pattern of Liver Depression and Qi Stagnation (LDQS)' or'pattern of Deficiency of Both Heart and Spleen (DBHS)
2. The severity of the symptoms is moderate or severe, confirmed by a 35 or greater of Hamilton Rating Scale for Depression(HAMD) score
3. Absence of brain and/or severe physical diseases
4. 18-65years old

Exclusion Criteria:

1. In pregnancy，brain and other severe medical conditions
2. Psychoactive substance abuse
3. Had a diagnosis of bipolar disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: LDQS group; Liver Depression and Qi Stagnation (LDQS)group,Liver Depression and Qi Stagnation Syndrome should include at least the following 5 symptoms and signs: emotional depression or sadness, pessimism, short breath, sigh, dysphoria，thin coating，stringy pulse Drugs use generic name :Venlafaxine; Dosage form:capsule Dosage, frequency and duration:Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline and after 6-week venlafaxine administration.	Drug: venlafaxine; Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. Patients were prescribed a combination of venlafaxine and Benzodiazepines for sleep disturbance.; Other Names: clonazepam
Active Comparator: DBHS group; Deficiency of Both Heart and Spleen (DBHS) group,Deficiency of Both Heart and Spleen Syndrome should include at least following 6 symptoms and signs: emotional depression, thinking torpidity, tiredness, forgetfulness, insomnia, loose stool, sweating, pale tongue body, thin tongue coating, and thin and deep pulse Drugs use generic name :Venlafaxine; Dosage form:capsule Dosage, frequency and duration:Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline and after 6-week .	Drug: venlafaxine; Venlafaxine dose was initiated at 75 mg/day and escalated to an optimal dose (150-225 mg/day in most cases) within 2 week, depending upon individual patient response, but the maximum dose could not exceed 300 mg/day during the next 4 weeks. Patients were prescribed a combination of venlafaxine and Benzodiazepines for sleep disturbance.; Other Names: clonazepam
No Intervention: the normal controls group; The normal controls group including the healthy volunteer None drug The biomarkers of neurobiochemistry, metabonomics and neuroimaging would be tested at the baseline .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain neuroimaging	Diffusion Tensor Imaging(DTI) is used to detect changes in FA maps of brain white matter fiber in major depressive patients	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical tests	Gas Chromatography-Mass Spectrum is used to test blood and urine samples for: lactic acid, alanine, 3 - hydroxy butyric acid, valine, carbamide, glycerinum, phosphoric acid, isoleucine, glycine, succinic acid, threonine, malic acid, glutamic acid, citric acid, stearic acid, GABA, methionine, cysteine, lysine, tryptophan, leucine, methionine and tyrosine.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurochemical tests	High Performance Liquid Chromatography (HPLC) is used to detect blood samples for: 5-HT, NE, DA, 5-HTAA, and HVA.	2 years

Collaborators and Investigators

• Sponsor: Zhejiang Provincial Tongde Hospital
• Collaborators: The University of Hong Kong
• Investigators: Study Director: Lan-ying Liu, Master, Zhejiang Provincial Tongde Hospital

Publications and helpful links

General Publications

• Liu LY, Xu XP, Luo LY, Zhu CQ, Li YP, Wang PR, Zhang YY, Yang CY, Hou HT, Cao YL, Wang G, Hui ES, Zhang ZJ. Brain connectomic associations with traditional Chinese medicine diagnostic classification of major depressive disorder: a diffusion tensor imaging study. Chin Med. 2019 Apr 11;14:15. doi: 10.1186/s13020-019-0239-8. eCollection 2019.
• Liu LY, Zhang HJ, Luo LY, Pu JB, Liang WQ, Zhu CQ, Li YP, Wang PR, Zhang YY, Yang CY, Zhang ZJ. Blood and urinary metabolomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder. Chin Med. 2018 Oct 25;13:53. doi: 10.1186/s13020-018-0211-z. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: December 18, 2014
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Estimate): April 27, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: neuroimaging; Neurological; metabonomics; major depression disorder; biochemistry; TCM diagnosis
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; GABA Modulators; GABA Agents; Anticonvulsants; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Clonazepam
• Other Study ID Numbers: zjsltdyy2014009; 8140151401 (Other Grant/Funding Number: National Natural Science Foundation of China)