Pharmacogenomics on Individualized Precise Treatment of Patients With Depression

• ClinicalTrials.gov Identifier: NCT05669391
• Recruitment Status: Not yet recruiting
• First Posted: December 30, 2022
• Last Update Posted: January 3, 2023
• Sponsor: Tongji University
• Information provided by (Responsible Party): Jie Tong, Tongji University

Tracking Information

• First Submitted Date: December 20, 2022
• First Posted Date: December 30, 2022
• Last Update Posted Date: January 3, 2023
• Estimated Study Start Date: January 1, 2023
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2022)

• Genomic analysis of antidepressants [ Time Frame: Baseline ]
  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.
• 17-items Hamilton Depression Scale [ Time Frame: Baseline ]
  Evaluate the severity and treatment effect of the patient's depression within one week.
• 17-items Hamilton Depression Scale [ Time Frame: Week 4 ]
  Evaluate the severity and treatment effect of the patient's depression within one week.
• 17-items Hamilton Depression Scale [ Time Frame: Week 8 ]
  Evaluate the severity and treatment effect of the patient's depression within one week.
• 17-items Hamilton Depression Scale [ Time Frame: Week 16 ]
  Evaluate the severity and treatment effect of the patient's depression within one week.
• 17-items Hamilton Depression Scale [ Time Frame: Week 32 ]
  Evaluate the severity and treatment effect of the patient's depression within one week.
• Dimensional Anhedonia Rating Scale [ Time Frame: Baseline ]
  Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.
• Dimensional Anhedonia Rating Scale [ Time Frame: Week 4 ]
  Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.
• Dimensional Anhedonia Rating Scale [ Time Frame: Week 8 ]
  Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.
• Dimensional Anhedonia Rating Scale [ Time Frame: Week 16 ]
  Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.
• Dimensional Anhedonia Rating Scale [ Time Frame: Week 32 ]
  Assess the patient's level of interest, motivation, effort, and happiness in experiencing pleasant activities or experiences.
• Antidepressant Side-Effect Checklist [ Time Frame: Baseline ]
  Evaluate the adverse reactions of patients after using antidepressants.
• Antidepressant Side-Effect Checklist [ Time Frame: Week 4 ]
  Evaluate the adverse reactions of patients after using antidepressants.
• Antidepressant Side-Effect Checklist [ Time Frame: Week 8 ]
  Evaluate the adverse reactions of patients after using antidepressants.
• Antidepressant Side-Effect Checklist [ Time Frame: Week 16 ]
  Evaluate the adverse reactions of patients after using antidepressants.
• Antidepressant Side-Effect Checklist [ Time Frame: Week 32 ]
  Evaluate the adverse reactions of patients after using antidepressants.
• Perceived deficits questionnaire [ Time Frame: Baseline ]
  Assess the patient's subjective cognitive function within one week.
• Perceived deficits questionnaire [ Time Frame: Week 4 ]
  Assess the patient's subjective cognitive function within one week.
• Perceived deficits questionnaire [ Time Frame: Week 8 ]
  Assess the patient's subjective cognitive function within one week.
• Perceived deficits questionnaire [ Time Frame: Week 16 ]
  Assess the patient's subjective cognitive function within one week.
• Perceived deficits questionnaire [ Time Frame: Week 32 ]
  Assess the patient's subjective cognitive function within one week.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 20, 2022)

• Hamilton Anxiety Scale [ Time Frame: Baseline ]
  Assess the severity of the patient's anxiety symptoms.
• Hamilton Anxiety Scale [ Time Frame: Week 4 ]
  Assess the severity of the patient's anxiety symptoms.
• Hamilton Anxiety Scale [ Time Frame: Week 8 ]
  Assess the severity of the patient's anxiety symptoms.
• Hamilton Anxiety Scale [ Time Frame: Week 16 ]
  Assess the severity of the patient's anxiety symptoms.
• Hamilton Anxiety Scale [ Time Frame: Week 32 ]
  Assess the severity of the patient's anxiety symptoms.
• Pittsburgh sleep quality index [ Time Frame: Baseline ]
  Evaluate the patient's sleep quality within one month, including sleep effect and duration.
• Pittsburgh sleep quality index [ Time Frame: Week 4 ]
  Evaluate the patient's sleep quality within one month, including sleep effect and duration.
• Pittsburgh sleep quality index [ Time Frame: Week 8 ]
  Evaluate the patient's sleep quality within one month, including sleep effect and duration.
• Pittsburgh sleep quality index [ Time Frame: Week 16 ]
  Evaluate the patient's sleep quality within one month, including sleep effect and duration.
• Pittsburgh sleep quality index [ Time Frame: Week 32 ]
  Evaluate the patient's sleep quality within one month, including sleep effect and duration.
• Short-form 36 item health survey questionnaire [ Time Frame: Baseline ]
  Assess the patient's health and quality of life within one month
• Short-form 36 item health survey questionnaire [ Time Frame: Week 4 ]
  Assess the patient's health and quality of life within one month
• Short-form 36 item health survey questionnaire [ Time Frame: Week 8 ]
  Assess the patient's health and quality of life within one month
• Short-form 36 item health survey questionnaire [ Time Frame: Week 16 ]
  Assess the patient's health and quality of life within one month
• Short-form 36 item health survey questionnaire [ Time Frame: Week 32 ]
  Assess the patient's health and quality of life within one month

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacogenomics on Individualized Precise Treatment of Patients With Depression
• Official Title: Randomized Controlled Study on the Effect of Pharmacogenomics on Individualized Precise Treatment of Patients With Depression
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Health Services Research

Condition

• Pharmacogenomics
• Depression

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.

Study Arms

• Experimental: Pharmacogenomics Group
  Intervention: Diagnostic Test: Genomic analysis of antidepressants
• No Intervention: Non Pharmacogenomics Group

Publications *

• 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. doi: 10.1515/CCLM.1998.165.
• 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. doi: 10.4088/JCP.19m12949.
• 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/s00213-020-05550-8. Epub 2020 Jun 11.
• 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 depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res. 2019 Apr;111:59-67. doi: 10.1016/j.jpsychires.2019.01.003. Epub 2019 Jan 4.
• 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.
• 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, Sadee W, Klein TE, Johnson JA, Relling MV, Wang L, Weinshilboum RM, Shuldiner AR, Freimuth RR; Pharmacogenomics Research Network Translational Pharmacogenetics Program. The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems. Clin Pharmacol Ther. 2017 Sep;102(3):502-510. doi: 10.1002/cpt.630. Epub 2017 Jun 9.
• 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.
• 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: 10.3389/fphar.2019.00099. eCollection 2019.
• 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 Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:28-34. doi: 10.1016/j.pnpbp.2016.12.003. Epub 2016 Dec 23.
• 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.

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: December 20, 2022): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Xirong Sun, M.D.; 86-2168306699; xirongsun@163.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT05669391
• Other Study ID Numbers: PWZxk2022-18
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jie Tong, Tongji University
• Original Responsible Party: Jie Tong, Tongji University, M.D.
• Current Study Sponsor: Tongji University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Tongji University
• Verification Date: December 2022