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Trial record 25 of 1107 for:    pharmacogenomics OR pharmacogenetics

Pharmacogenetics Informed Tricyclic Antidepressant Dosing (PITA) (PITA)

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ClinicalTrials.gov Identifier: NCT03548675
Recruitment Status : Recruiting
First Posted : June 7, 2018
Last Update Posted : September 13, 2019
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE May 23, 2018
First Posted Date  ICMJE June 7, 2018
Last Update Posted Date September 13, 2019
Actual Study Start Date  ICMJE May 23, 2018
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
Time to TCA plasma concentration in the therapeutic range [ Time Frame: During the 7 weeks treatment phase ]
Time to TCA plasma concentration in the therapeutic range
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03548675 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2018)
  • Reduction of depressive symptoms [ Time Frame: Difference between measurements at baseline and after 7 weeks of treatment ]
    HAM-D reduction
  • Highest level of side effects [ Time Frame: During the 7 weeks treatment phase ]
    summary measure: FIBSER
  • Economic Evaluation (Cost Effectiveness) [ Time Frame: 26 weeks after the start of treatment ]
    Utility based on EQ5D5L measurement
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacogenetics Informed Tricyclic Antidepressant Dosing (PITA)
Official Title  ICMJE Pharmacogenetics to Improve Personalized Antidepressant Dosing in Patients With Severe Depression;a Randomized Controlled Trial Using Tricyclic Antidepressants
Brief Summary Tricyclic Antidepressants (TCA's) are the cornerstone of treatment for patients with severe Major Depressive Disorder (sMDD). Current dosing is guided by repeated measurements of blood levels. Compared to patients with a normal metabolization function, for those with increased CYP450 enzyme activity it takes longer to reach a therapeutic drug level. The consequent delay of drug efficacy is associated with a prolonged treatment period, increased risk of suicidal behaviour and eventually lower remission rates. For those with reduced CYP450 activity higher rates of side effects are expected. An innovative TCA dosing strategy, taking the genetic variants of CYP2D6 and CYP2C19 into account may help to reduce the above mentioned problems. Up till now, the current guidelines for CYP450 pharmacogenetics based TCA dosing have not been systematically evaluated for effectiveness and cost-effectiveness in larger groups of patients. Such evaluation is necessary before broad implementation of these guidelines can be advocated. In the present study 200 patients with sMDD who are treated with nortriptyline, clomipramine or imipramine, with genotypes associated with deviant CYP450 metabolizer status are randomized over two strategies: dosing based both on CYP450-genotype and blood level measurements and dosing as usual (standard doses plus blood levels). A third arm of 100 patients with normal CYP450-activity serves as a reference group (standard dosing and blood levels). We hypothesize that for patients with genotypes reflecting deviant CYP450 enzyme activity, genotype informed dosing results in faster attainment of therapeutic drug levels, lower rates of side effects, earlier symptom relief and lower levels of health- and working related costs.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This study is a randomized controlled clinical trial.
Masking: Single (Outcomes Assessor)
Masking Description:
Prescribing physicians will be unblinded for the genotype and the resulting metabolization phenotype. Outcome assessments will be performed by blinded researchers and the patients themselves (self-assessments).
Primary Purpose: Treatment
Condition  ICMJE Depressive Disorder, Major
Intervention  ICMJE Drug: TCA treatment
All patients fulfilling inclusion criteria will be genotyped for CYP2C19 and CYP2D6 genes. Based on the genetic test results patients will be classified into a metabolisation phenotype (UM, EM, IM or PM).
Study Arms  ICMJE
  • Experimental: Genotype-guided TCA treatment
    Genotype guided dosing of the TCAs in patients with a PM,IM or UM phenotype based on pharmacogenetic test.
    Intervention: Drug: TCA treatment
  • Active Comparator: Standard TCA treatment (PM,IM or UM)
    Standard dosing of TCA in patients with a PM,IM or UM phenotype based on pharmacogenetic test
    Intervention: Drug: TCA treatment
  • Active Comparator: Standard TCA treatment (EM)
    Standard dosing of TCA in patients with EM phenotype based on pharmacogenetic test
    Intervention: Drug: TCA treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2018)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients are in- and outpatients, having a primary diagnosis of severe major depressive disorder (SCID-I diagnosis in agreement with DSM-5 criteria and a Hamilton Rating Scale for Depression score ≥ 19 (HAM-D-17-item version), aged 18-65 years, who, according to their physician, are eligible for treatment with a TCA (Nortriptyline (NOR), Clomipramine (CLOMI) or Imipramine (IMI)). The choice of the specific TCA is at the discretion of the physician in attendance.

Exclusion Criteria:

  1. Psychotic depression
  2. Bipolar I or II disorder.
  3. Schizophrenia or other primary psychotic disorder.
  4. Drug or alcohol dependence in the past 3 months.
  5. Mental Retardation (IQ < 80).
  6. For women: pregnancy or possibility for pregnancy without adequate contraceptive measures.
  7. Breastfeeding.
  8. Serious medical illness affecting the CNS, including but not restricted to M Parkinson, SLE, brain tumour, CVA.
  9. Relevant medical illness as contra-indication for TCA use, such as recent myocardial infarction.
  10. Other drugs influencing the pharmacokinetics of the TCAs as based on a list of interacting drugs. In case of psychotropic co-medication only a benzodiazepine in a dose equivalent up to 4 mg lorazepam will be allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joost Janzing, MD PhD +31-(0)243613489 Joost.Janzing@radboudumc.nl
Contact: Marieke Coenen, PhD +31-(0)243617752 Marieke.Coenen@radboudumc.nl
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03548675
Other Study ID Numbers  ICMJE 848016004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE ZonMw: The Netherlands Organisation for Health Research and Development
Investigators  ICMJE
Principal Investigator: Joost Janzing, MD PhD Radboudumc dept of Psychiatry
PRS Account Radboud University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP