Association of Peripheral Immune Cells With Antidepressant Treatment Response

Depressive Disorder Clinical Trial

Official title:

Association of Peripheral Immune Cells With Antidepressant Treatment Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06182722
• Other study ID #: 2022-TX-010
• Status: Recruiting
• Start date: March 13, 2024
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Shanghai Mental Health Center
• Contact: Huangfang Li
• Phone: +86-2134773128
• Email: lihuafang[@]smhc.org.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this observational study is discovering potential biomarkers to predict antidepressant treatment response in patients with major depressive disorder (MDD) while comparing the transcriptomic changes between patients with MDD and healthy controls as well as before and after antidepressant treatment.

Eligible patients will be assessed at Week 1, Week 2, Week 4 and Week 8 while healthy normal volunteers will only be evaluated at baseline. Assessments will include the following: an interview about mental and physical health, a physical examination including drawing of venous blood samples and several psychiatric rating scales.

Description:

This study is focusing on evaluating the peripheral immune system of major depressive disorder (MDD) and the impact of antidepressants treatment. Single-cell RNA sequencing and single-cell VDJ sequencing will be performed on peripheral blood mononuclear cells to collect transcriptome information and immune repertoire of peripheral blood in patients with MDD. Bulk RNA sequencing and flow cytometry will be used to validate the clinical value of results.

This is a biomarker study (antidepressants); treatment will be carried out according to physicians' orders.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 18-65 years old, regardless of gender;

2. The subject is an outpatient/inpatient and meets DSM-5 diagnostic criteria of current or past major depressive disorder;

3. SSRIs or SNRIs monotherapy;

4. HAMD-17 total score = 18 at baseline;

5. The subject can read and write and is capable of giving informed consent.

Exclusion Criteria:

1. Patients with mental illness other than MDD;

2. Patients with liver and kidney diseases, cardiovascular system diseases, cancer, diabetes, thyroid diseases or other serious or unstable conditions;

3. Previous organic brain disease, traumatic brain injury or other diseases that can cause structural brain changes;

4. Serious abnormalities indicated by laboratory tests or electrocardiograms;

5. Alcohol or drug addiction;

6. Suffering from systemic lupus erythematosus, multiple sclerosis or other autoimmune diseases;

7. Patients who are taking drugs that directly impact on the immune system such as anti-inflammatory drugs or immunosuppressants;

8. Patients who have taken antidepressants or other antipsychotics within 2 weeks before enrollment;

9. Patients who have received MECT or systematic psychotherapy within 3 months before enrollment;

10. Patients at high risk of suicide, or reporting a HAMD-17 item 3 (suicide item) score >3 at baseline;

11. Subjects who are pregnant or lactating;

12. Other conditions that are considered not suitable for participating in the research.

Related Conditions & MeSH terms

• Depressive Disorder
• Genetic Change

Intervention

Diagnostic Test:
• Mental assessments
Patients will receive psychiatric rating scales evaluation every visit.

Locations

Country	Name	City	State
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Mental Health Center

Country where clinical trial is conducted

China, 

References & Publications (6)

Cattaneo A, Ferrari C, Turner L, Mariani N, Enache D, Hastings C, Kose M, Lombardo G, McLaughlin AP, Nettis MA, Nikkheslat N, Sforzini L, Worrell C, Zajkowska Z, Cattane N, Lopizzo N, Mazzelli M, Pointon L, Cowen PJ, Cavanagh J, Harrison NA, de Boer P, Jones D, Drevets WC, Mondelli V, Bullmore ET; Neuroimmunology of Mood Disorders and Alzheimer's Disease (NIMA) Consortium; Pariante CM. Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study. Transl Psychiatry. 2020 Jul 23;10(1):232. doi: 10.1038/s41398-020-00874-7. Erratum In: Transl Psychiatry. 2020 Oct 19;10(1):352. — View Citation

Kato T, Furukawa TA, Mantani A, Kurata K, Kubouchi H, Hirota S, Sato H, Sugishita K, Chino B, Itoh K, Ikeda Y, Shinagawa Y, Kondo M, Okamoto Y, Fujita H, Suga M, Yasumoto S, Tsujino N, Inoue T, Fujise N, Akechi T, Yamada M, Shimodera S, Watanabe N, Inagaki M, Miki K, Ogawa Y, Takeshima N, Hayasaka Y, Tajika A, Shinohara K, Yonemoto N, Tanaka S, Zhou Q, Guyatt GH; SUN?D Investigators. Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN?D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial. BMC Med. 2018 Jul 11;16(1):103. doi: 10.1186/s12916-018-1096-5. — View Citation

Leday GGR, Vertes PE, Richardson S, Greene JR, Regan T, Khan S, Henderson R, Freeman TC, Pariante CM, Harrison NA; MRC Immunopsychiatry Consortium; Perry VH, Drevets WC, Wittenberg GM, Bullmore ET. Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder. Biol Psychiatry. 2018 Jan 1;83(1):70-80. doi: 10.1016/j.biopsych.2017.01.021. Epub 2017 Jul 6. — View Citation

Malhi GS, Mann JJ. Depression. Lancet. 2018 Nov 24;392(10161):2299-2312. doi: 10.1016/S0140-6736(18)31948-2. Epub 2018 Nov 2. — View Citation

Nohr AK, Lindow M, Forsingdal A, Demharter S, Nielsen T, Buller R, Moltke I, Vitezic M, Albrechtsen A. A large-scale genome-wide gene expression analysis in peripheral blood identifies very few differentially expressed genes related to antidepressant treatment and response in patients with major depressive disorder. Neuropsychopharmacology. 2021 Jun;46(7):1324-1332. doi: 10.1038/s41386-021-01002-9. Epub 2021 Apr 8. — View Citation

Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, Liu Z, Dong M, Hu X, Ouyang W, Peng J, Zhang Z. Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. Cell. 2017 Jun 15;169(7):1342-1356.e16. doi: 10.1016/j.cell.2017.05.035. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HAMD-17 (Hamilton Depression Rating Scale) total score	Minimun value of HAMD-17 (Hamilton Depression Rating Scale) is 0 and maximum value of HAMD-17 is 68 points. Higher scores implies higher severity.	Baseline, Week 2, Week 4 and Week 8.
Other	MADRS (Montgomery-Åsberg depression rating scale) total score	Minimun value of MADRS (Montgomery-Åsberg depression rating scale) is 0 and maximum value of MADRS is 60 points. Higher scores implies higher severity.	Baseline, Week 2, Week 4 and Week 8.
Other	CGI-S (Clinical Gloabl Impression-Severity) score	Minimun value of CGI-S (Clinical Gloabl Impression-Severity) is 0 and maximum value of CGI-S is 7 points. Higher scores implies higher severity.	Baseline, Week 2, Week 4 and Week 8.
Other	CGI-I (Clinical Gloabl Impression-Improvement) score	Minimun value of CGI-I (Clinical Gloabl Impression-Improvement) is 1 points and maximum value of CGI-I is 7 points. Higher scores implies worse outcome.	Baseline, Week 2, Week 4 and Week 8.
Primary	Change of HAMD-17 (Hamilton Depression Rating Scale) total score	The overall score of HAMD-17 (Hamilton Depression Rating Scale) is 68 points. Primary outcome measures the change of HAMD-17 total score between baseline and week 8. Larger reduction in HAMD-17 represents better antidepressant treatment response.	From baseline to Week 8
Secondary	Effective rate measured by HAMD-17 (Hamilton Depression Rating Scale)	A reduction of 50% or more in the HAMD-17 (Hamilton Depression Rating Scale) total score. More patients with a reduction of 50% or more indicates better effectiveness. Minimun value of HAMD-17 is 0 and maximum value of HAMD-17 is 68 points.	From baseline to Week 8
Secondary	MADRS Effective rate measured by MADRS (Montgomery-Åsberg depression rating scale)	A reduction of 50% or more in the MADRS (Montgomery-Åsberg depression rating scale) total score. More patients with a reduction of 50% or more indicates better effectiveness. Minimun value of MADRS is 0 and maximum value of MADRS is 60 points.	From baseline to Week 8
Secondary	Remission rate measured by HAMD-17 (Hamilton Depression Rating Scale)	HAMD-17 (Hamilton Depression Rating Scale) total score =10 at week8. Lower total score of HAMD-17 at week 8 indicates better outcome. Minimun value of HAMD-17 is 0 and maximum value of HAMD-17 is 68 points.	From baseline to Week 8
Secondary	MADRS Remission rate measured by MADRS (Montgomery-Åsberg depression rating scale)	MADRS (Montgomery-Åsberg depression rating scale) total score =7 at week8. Lower total score of HAMD-17 at week 8 indicates better outcome. Minimun value of MADRS is 0 and maximum value of MADRS is 60 points.	From baseline to Week 8