Pharmacogenomics on Individualized Precise Treatment of Patients With Depression

Depression Clinical Trial

Official title:

Randomized Controlled Study on the Effect of Pharmacogenomics on Individualized Precise Treatment of Patients With Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05669391
• Other study ID #: PWZxk2022-18
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2022
• Source: Tongji University
• Contact: Xirong Sun, M.D.
• Phone: 86-2168306699
• Email: xirongsun[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Based on pharmacogenomics analysis technology, this topic explored its impact on individualized precise treatment of patients with depression through randomized controlled trials. The study subjects were depression patients from the mental health research center affiliated to Tongji University. The sample size was estimated by PASS 21.0.3 software. The sample size of the intervention group and the control group was 60 cases each, and SPSS 25.0 software was used for random sampling. The intervention group completed the pharmacogenomic analysis of antidepressants before using them, and selected appropriate antidepressants according to the characteristics of pharmacokinetics and pharmacodynamics of individual patients, while the control group was administered according to routine treatment. 17 items Hamilton Compression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), Dimensional Anhedonia Rating Scale (DARS), Pittsburgh sleep quality index (PSQI), Antidepressant Side Effect Checklist (ASEC), Short form 36 item health survey questionnaire (SF-36) (PDQ) assessment. R Project 4.1.1 software was used for statistical analysis of data, PLink v1.07 and Haploview software were used for association analysis of whole genome and drug efficacy and adverse reactions. To explore the difference between the reduction rate of drug efficacy and adverse reactions in patients with depression after pharmacogenomics intervention and conventional treatment. At the same time, we verified and found the gene loci related to the efficacy and adverse reactions of antidepressants in the East Asian population.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Both biological parents are Chinese nationals;

2. Conform to the diagnostic criteria of depression in the fifth edition of the American Diagnostic and Statistical Manual of Mental Disorders (DSM-5);

3. The total score of 17 items of Hamilton Depression Scale (HAMD-17) is = 17;

4. Never used relevant antidepressant drugs;

5. Have a certain visual and auditory discrimination, and have no understanding obstacle;

6. Be able to independently complete the scale measurement;

7. Education level above primary school;

8. Obtain the written informed consent of the patient. If the patient is incapacitated during the onset of the disease, the written informed consent of the legal guardian is required.

Exclusion Criteria:

1. Patients with schizophrenia, schizoaffective disorder, bipolar affective disorder, mental retardation, generalized developmental disorder, delirium, dementia, cognitive dysfunction, alcohol dependence and other diagnoses;

2. Suffering from serious organic diseases, such as diabetes, thyroid disease, hypertension, cardiovascular disease, brain injury, cerebral ischemia or hemorrhage;

3. Patients with narrow angle glaucoma;

4. History of epilepsy and febrile convulsion;

5. Those who have taken drugs in the past;

6. Syphilis specific antibody and AIDS antibody are positive;

7. Those who received MECT or rTMS and other neuromodulation therapy one month before enrollment;

8. The risk assessment indicates that there is a serious suicide attempt or excitement;

9. Laboratory examination indicates that liver function and renal function are impaired;

10. Pregnant or lactating women, or those who plan to have a pregnancy in the near future;

11. Other contraindications of antidepressants.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Pharmacogenomics

Intervention

Diagnostic Test:
• Genomic analysis of antidepressants
Genomic analysis of all antidepressants. Tris EDTA anticoagulation and salting out were used to extract DNA. OD 260/280 was between 1.6-1.8 and the concentration was greater than 50 ng/ µ L? Using the PCR gene chip detection method and the Asian Screening Array (ASA) chip detection technology of Illumina Company (this chip is the first whole genome SNP chip designed based on the whole genome sequencing data of 9000+East Asian populations, which contains 750000 markers, with 85% of the effective loci), we can obtain the genetic information of polymorphic loci related to the individual differences of drug effects of subjects.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tongji University

References & Publications (10)

Ahmadimanesh M, Balarastaghi S, Rashedinia M, Yazdian-Robati R. A systematic review on the genotoxic effect of serotonin and norepinephrine reuptake inhibitors (SNRIs) antidepressants. Psychopharmacology (Berl). 2020 Jul;237(7):1909-1915. doi: 10.1007/s00 — View Citation

Aldrich SL, Poweleit EA, Prows CA, Martin LJ, Strawn JR, Ramsey LB. Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders. Front Pharmacol. 2019 Feb 19;10:99. doi: 10.33 — View Citation

Cremonesi L, Carrera P, Cardillo E, Fumagalli A, Lucchiari S, Ferrari M, Righetti SC, Righetti PG, Gelfi C. Optimized detection of DNA point mutations by double gradient denaturing gradient gel electrophoresis. Clin Chem Lab Med. 1998 Dec;36(12):959-61. d — View Citation

Gasso P, Rodriguez N, Blazquez A, Monteagudo A, Boloc D, Plana MT, Lafuente A, Lazaro L, Arnaiz JA, Mas S. Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine. Prog Neuropsychophar — View Citation

Greden JF, Parikh SV, Rothschild AJ, Thase ME, Dunlop BW, DeBattista C, Conway CR, Forester BP, Mondimore FM, Shelton RC, Macaluso M, Li J, Brown K, Gilbert A, Burns L, Jablonski MR, Dechairo B. Impact of pharmacogenomics on clinical outcomes in major dep — View Citation

Hattinger CM, Patrizio MP, Luppi S, Serra M. Pharmacogenomics and Pharmacogenetics in Osteosarcoma: Translational Studies and Clinical Impact. Int J Mol Sci. 2020 Jun 30;21(13):4659. doi: 10.3390/ijms21134659. — View Citation

Health Quality Ontario. Pharmacogenomic Testing for Psychotropic Medication Selection: A Systematic Review of the Assurex GeneSight Psychotropic Test. Ont Health Technol Assess Ser. 2017 Apr 11;17(4):1-39. eCollection 2017. — View Citation

Luzum JA, Pakyz RE, Elsey AR, Haidar CE, Peterson JF, Whirl-Carrillo M, Handelman SK, Palmer K, Pulley JM, Beller M, Schildcrout JS, Field JR, Weitzel KW, Cooper-DeHoff RM, Cavallari LH, O'Donnell PH, Altman RB, Pereira N, Ratain MJ, Roden DM, Embi PJ, Sa — View Citation

Rush AJ, South C, Jha MK, Jain SB, Trivedi MH. What to Expect When Switching to a Second Antidepressant Medication Following an Ineffective Initial SSRI: A Report From the Randomized Clinical STAR*D Study. J Clin Psychiatry. 2020 Aug 11;81(5):19m12949. do — View Citation

Winner JG, Carhart JM, Altar CA, Allen JD, Dechairo BM. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med. 2013 Nov;16(89):219-27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genomic analysis of antidepressants	Using PCR gene chip detection method and Asian Screening Array (ASA) chip detection technology of Illumina Company, we can obtain the genetic information of polymorphic sites related to the individual differences of drug effects of subjects.	Baseline
Primary	17-items Hamilton Depression Scale	Evaluate the severity and treatment effect of the patient's depression within one week.	Baseline
Primary	17-items Hamilton Depression Scale	Evaluate the severity and treatment effect of the patient's depression within one week.	Week 4
Primary	17-items Hamilton Depression Scale	Evaluate the severity and treatment effect of the patient's depression within one week.	Week 8
Primary	17-items Hamilton Depression Scale	Evaluate the severity and treatment effect of the patient's depression within one week.	Week 16
Primary	17-items Hamilton Depression Scale	Evaluate the severity and treatment effect of the patient's depression within one week.	Week 32
Primary	Dimensional Anhedonia Rating Scale	Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.	Baseline
Primary	Dimensional Anhedonia Rating Scale	Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.	Week 4
Primary	Dimensional Anhedonia Rating Scale	Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.	Week 8
Primary	Dimensional Anhedonia Rating Scale	Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.	Week 16
Primary	Dimensional Anhedonia Rating Scale	Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.	Week 32
Primary	Antidepressant Side-Effect Checklist	Evaluate the adverse reactions of patients after using antidepressants.	Baseline
Primary	Antidepressant Side-Effect Checklist	Evaluate the adverse reactions of patients after using antidepressants.	Week 4
Primary	Antidepressant Side-Effect Checklist	Evaluate the adverse reactions of patients after using antidepressants.	Week 8
Primary	Antidepressant Side-Effect Checklist	Evaluate the adverse reactions of patients after using antidepressants.	Week 16
Primary	Antidepressant Side-Effect Checklist	Evaluate the adverse reactions of patients after using antidepressants.	Week 32
Primary	Perceived deficits questionnaire	Assess the patient's subjective cognitive function within one week.	Baseline
Primary	Perceived deficits questionnaire	Assess the patient's subjective cognitive function within one week.	Week 4
Primary	Perceived deficits questionnaire	Assess the patient's subjective cognitive function within one week.	Week 8
Primary	Perceived deficits questionnaire	Assess the patient's subjective cognitive function within one week.	Week 16
Primary	Perceived deficits questionnaire	Assess the patient's subjective cognitive function within one week.	Week 32
Secondary	Hamilton Anxiety Scale	Assess the severity of the patient's anxiety symptoms.	Baseline
Secondary	Hamilton Anxiety Scale	Assess the severity of the patient's anxiety symptoms.	Week 4
Secondary	Hamilton Anxiety Scale	Assess the severity of the patient's anxiety symptoms.	Week 8
Secondary	Hamilton Anxiety Scale	Assess the severity of the patient's anxiety symptoms.	Week 16
Secondary	Hamilton Anxiety Scale	Assess the severity of the patient's anxiety symptoms.	Week 32
Secondary	Pittsburgh sleep quality index	Evaluate the patient's sleep quality within one month, including sleep effect and duration.	Baseline
Secondary	Pittsburgh sleep quality index	Evaluate the patient's sleep quality within one month, including sleep effect and duration.	Week 4
Secondary	Pittsburgh sleep quality index	Evaluate the patient's sleep quality within one month, including sleep effect and duration.	Week 8
Secondary	Pittsburgh sleep quality index	Evaluate the patient's sleep quality within one month, including sleep effect and duration.	Week 16
Secondary	Pittsburgh sleep quality index	Evaluate the patient's sleep quality within one month, including sleep effect and duration.	Week 32
Secondary	Short-form 36 item health survey questionnaire	Assess the patient's health and quality of life within one month	Baseline
Secondary	Short-form 36 item health survey questionnaire	Assess the patient's health and quality of life within one month	Week 4
Secondary	Short-form 36 item health survey questionnaire	Assess the patient's health and quality of life within one month	Week 8
Secondary	Short-form 36 item health survey questionnaire	Assess the patient's health and quality of life within one month	Week 16
Secondary	Short-form 36 item health survey questionnaire	Assess the patient's health and quality of life within one month	Week 32