Clinical trial NCT04615234: Clinical Validation of a Combinatorial Pharmacogenomic Approach in Major Depressive Disorder
Official title: Towards Precision Medicine in Psychiatry: Clinical Validation of a Combinatorial Pharmacogenomic Approach.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Major Depressive Disorder
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
Collaborators: name: IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli
First posted: 2020-11-04
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: MDD out-patients are voluntarily enrolling in the study. Patients referred to psychiatric services due to the failure and/or the onset of adverse effects of their current treatment for receiving a new AD.

Brief summary: Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder causing serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment choice; however, only about one third of patients respond to the first trial because of antidepressants ineffectiveness or side-effects. This causes suffering for patients and their families and significantly contributes to pushing up costs for healthcare services. Precision medicine in psychiatry might offer to clinicians the possibility to tailor the treatment according to the best possible evidence of effectiveness and tolerability for each subject. In this context our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with an advocacy license independence.

Our study is a prospective single-blind randomized controlled clinical observational trial enrolling 300 MDD patients. Patients referred to psychiatric services due to the failure and/or the onset of adverse effects of their current treatment for receiving a new antidepressant. Eligible participants with a primary diagnosis of MDD according to DSM-5 criteria and a Hamilton Depression Rating Scale (HAM-D17) with a score \> 14 are randomized to TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, buccal brush for DNA is collected. The primary outcome is the reduction in depressive symptomatology as measured by HAM-D17. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks. This project represents the first randomized controlled clinical trial in which is tested whether a non-commercial PGx test improves outcomes in a MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test leading to a further cost-saving.


Eligibility criteria: Inclusion Criteria:

* A current diagnosis of unipolar depression according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)
* An Hamilton Depression Rating Scale (HAMD-17) score \>=14
* Caucasian ethnicity.

Exclusion Criteria:

* Cognitive impairment (Mini Mental State Examination MMSE \<24)
* Neurological disorders
* Diagnosis of MDD with psychotic features, bipolar I and II disorders, schizophrenia spectrum and other psychotic disorders, obsessive-compulsive disorder, post-traumatic stress disorder
* Substance abuse in the last 3 months
* Comorbidity with personality disorders (cluster A and/or B); pregnancy
* Comorbidity with other severe medical illness.

Primary outcomes:
measure: Clinical response
timeFrame: Baseline to 8 weeks
Secondary outcomes:
measure: Clinical response and remission
timeFrame: Baseline to 4 weeks, to 8 weeks and 12 weeks
Other outcomes:
measure: Clinical response and remission self-reported
timeFrame: Baseline to 4 weeks, to 8 weeks and 12 weeks
measure: Psychosocial functioning
timeFrame: Baseline to 8 weeks and 12 weeks
Locations:
city: Brescia
country: Italy
facility: Department of Mental Health and Addiction
state: BS
Study officials:
References:
citation: Minelli A, Barlati S, Vitali E, Bignotti S, Dattilo V, Tura GB, Maffioletti E, Giacopuzzi E, Santoro V, Perusi G, Cobelli C, Magri C, Bonizzato S, Bocchio-Chiavetto L, Spina E, Vita A, Gennarelli M. Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial). Trials. 2021 Dec 11;22(1):896. doi: 10.1186/s13063-021-05775-8.