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Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram (PGRN-SSRI)

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ClinicalTrials.gov Identifier: NCT00613470
Recruitment Status : Completed
First Posted : February 13, 2008
Last Update Posted : December 18, 2013
Sponsor:
Collaborators:
National Institute of General Medical Sciences (NIGMS)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Daniel K. Hall-Flavin, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE January 30, 2008
First Posted Date  ICMJE February 13, 2008
Last Update Posted Date December 18, 2013
Study Start Date  ICMJE March 2005
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2008)
The change in HRS-D17 will constitute the major research outcome measure used to assess drug response phenotype because it is widely used in psychiatric research, making it possible to perform comparisons with other studies. [ Time Frame: baseline, 4 week and 8 week visits ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00613470 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2008)
QIDS-C16 (obtained by the CRC), and the QIDS-SR16 [ Time Frame: week 0, 4, and 8 ]
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 Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Official Title  ICMJE Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Brief Summary

This study is one component of a larger U01 grant that was submitted in August, 2004 to the NIGMS as part of the Pharmacogenomic Research Network. This study will enroll 1200 patients over 4 years.

It is known that functionally significant genetic polymorphisms for the cytochrome P450 (CYPs) can contribute to individual differences in response to specific selective serotonin reuptake inhibitors (SSRIs). However, a better understanding of the pharmacogenomics of both PK and PD for SSRI antidepressants will inform clinical practice. Therefore, we propose to evaluate the contribution of pharmacogenomics to variation in response to the highly specific SSRIs citalopram (a racemic mixture) and escitalopram (a chiral compound containing the active S-isomer of citalopram ) by correlating both PK and PD variation for these agents with intragene haplotypes in genes encoding proteins involved in citalopram metabolism, as well as central nervous system (CNS) pathways for monoamine neurotransmitter biosynthesis, metabolism, storage, release, reuptake, and receptors. In the future this "candidate pathway" intragene haplotype genotyping strategy will also be complemented by the application of genome-wide screens performed with DNA from subjects with extreme phenotypes for response to citalopram.

Phenotypes to be measured before and after the initiation of citalopram or escitalopram therapy will include determinations of serum citalopram and metabolite concentrations, treatment response as measured by Hamilton Rating Scale for Depression indices, and number and severity of side effects as determined by structured questionnaires. The hypothesis to be tested is that inherited variation in citalopram metabolism and transport (PK) and/or PD variation as a result of inherited variation in monoamine neurotransmitter biosynthesis, metabolism, reuptake, storage, receptors or signaling contribute to individual variation in citalopram antidepressant efficacy and/or side effects.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Depression
Intervention  ICMJE Drug: citalopram and escitalopram

escitalopram tablets starting at 10 mg, increase to 20 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.

citalopram tablet or solution starting at 2o mg, increase to 40 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.

Study Arms  ICMJE Experimental: Citalopram and escitalopram

Citalopram tablet or solution starting at 20 mg, increase to 40 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.

Escitalopram tablets starting at 10 mg, increase to 20 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.

Intervention: Drug: citalopram and escitalopram
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: May 30, 2013)
927
Original Estimated Enrollment  ICMJE
 (submitted: January 30, 2008)
1200
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Outpatients or inpatients with nonpsychotic MDD.
  2. A score of >14 on the HRS-D17 (equivalent to 10 or greater on PHQ-9 which is used in primary care to assess depression) given that when medication exceeds the effect of placebo in primary care participants have a HRS-D17 >12. We added 2 HRS-D17 points to take into account the possibility of measurement error.
  3. Outpatients or inpatients for whom antidepressant treatment is deemed appropriate by the treating clinician.
  4. Subjects who are between 18-85 years of age.
  5. Participants who have general medical conditions (GMCs) which could conceivably be physiologically causing their depressive symptoms will receive treatment as usual for their GMCs as well as for their MDD.

Exclusion Criteria:

  • Subjects with medical contraindications that preclude citalopram or escitalopram treatment and those who have previously failed to respond to citalopram or escitalopram will be excluded. In addition, patients with schizophrenia, schizoaffective disorder, or who have Bipolar I disorder will be excluded because they have a primary psychiatric condition that requires a different initial treatment. Subjects currently on antidepressant medication with subtherapeutic results in terms of depression management will undergo a medication taper and discontinuation prior to initiation of citalopram or escitalopram treatment. The subject will be closely monitored by the primary physician or psychiatrist during the medication taper and discontinuation phase. The medication taper is left upto the treating physician's or psychiatrist's discretion. Study subjects who cannot be safely tapered from their medication or experience adverse effects during the taper will be excluded from the study. Study subjects using their antidepressant medication for management of nicotine dependence, chronic pain, migraine prophylaxis or other diagnoses will not be eligible for the study. Trazodone, Melatonin, and Diphenhydramine may be used as rescue medications for insomnia. Benzodiazepines may be used for treatment of anxiety and atomoxetine may be used for the treatment of attention deficit disorder. Study subjects currently on antipsychotic medications (e.g., typical and atypical antipsychotic drugs) and mood stabilizing agents (e.g., lithium, carbamazepine, valproate, lamotrigine, gabapentin, or other anticonvulsants) are not eligible for the study with the exception of those starting quetiapine after baseline. Subjects unable to give informed consent are excluded. Pregnant subjects will be excluded.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00613470
Other Study ID Numbers  ICMJE 170-05
U01GM061388 ( U.S. NIH Grant/Contract )
UL1RR024150 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Daniel K. Hall-Flavin, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE
  • National Institute of General Medical Sciences (NIGMS)
  • National Center for Research Resources (NCRR)
Investigators  ICMJE
Principal Investigator: Daniel K Hall-Flavin, M.D. Mayo Clinic
PRS Account Mayo Clinic
Verification Date December 2013

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