Trial record 12 of 3627 for:    "Depression" [DISEASE]

Brain Imaging, Genetics and Treatment for Major Depression

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01568684
First received: March 30, 2012
Last updated: March 11, 2014
Last verified: December 2012
  Purpose

Background:

- Antidepressants help many people with depression, however, some do not seem to benefit as much. Currently, it is not possible to determine who will improve with certain antidepressants. Studies have shown that genes may influence whether an antidepressant works for an individual. Other studies have shown that depressed people tend to have lower levels of a chemical called glutamate in parts of their brain, and that glutamate levels increase after recovering from depression. Researchers want to study the antidepressant citalopram (Celexa) to see how it affects glutamate levels in the brain. They also want to study how a person s genes affect their response to this treatment.

Objectives:

- To see whether glutamate levels and certain genes affect how a person responds to a particular antidepressant medication.

Eligibility:

- Individuals between 25 and 55 years of age who have been diagnosed with major depression (without psychotic features). Participants may not have tried more than three antidepressant treatments.

Design:

  • Participants will be screened with a physical exam and medical history. They will answer questions about mood and current feelings of depression, as well as family history of depression. Blood and urine samples will be collected.
  • This study will have two phases. The first phase may last up to 7 weeks depending on current antidepressant use and involves one to seven outpatient visits. The second phase lasts 8 weeks and involves five outpatient visits, one every 2 weeks.
  • In the first phase, participants will stop taking their current antidepressant medications for at least 2 weeks before the next phase of the study. Participants who are on fluoxetine (Prozac) will need to be off it for 6 weeks.
  • At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.
  • In the second phase, participants will take citalopram at the standard dose. They will answer questions about mood and response to the medication. They will also provide blood and saliva samples for tests.
  • At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.

Condition Intervention Phase
Depressive Disorder
Depressive Disorder, Major
Depression
Other: Citalopram
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacogenetics and Neuroimaging in Major Depressive Disorder (PAN-D)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Changes in prefrontal glutamate concentration after citalopram treatment.

Secondary Outcome Measures:
  • Changes in depressive symptoms after citalopram treatment.
  • Association between glutamate changes and genetic variation.

Enrollment: 0
Study Start Date: March 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: Citalopram
    Treatment
Detailed Description:

Objective:

Major depressive disorder (MDD) is a serious, debilitating, life-shortening illness that affects many persons of all ages and backgrounds. Although many patients suffering from MDD can expect improvement with antidepressant treatment, only a minority experience full remission, and little is known about the basis for individual differences in treatment outcome. The rationale for this study follows from the findings that treatment response in major depression is associated with: 1) variation in the genes encoding the serotonin 2A receptor (HTR2A) and the KA1 subunit of the glutamate-kainate receptor (GRIK4); and 2) increases in prefrontal glutamate/glutamine (glx) concentration measured by [+H] magnetic resonance spectroscopy (MRS). The central hypothesis is that genes associated with citalopram treatment outcome modulate glutamate concentrations in prefrontal brain (PFB) and thus facilitate response to citalopram treatment. Such information is important because it would ultimately allow the development of better treatments for MDD.

Study population:

A total of 104 moderate to severe MDD outpatients aged 25-55 with a baseline 17-item Hamilton Depression Rating Scale (HDRS) score of greater than or equal to18 who meet DSM-IV criteria for non-psychotic major depressive disorder (MDD) will be enrolled in the course of the study.

Design:

Subjects will be screened with an on-site research psychiatric evaluation using a structured interview (MINI plus). After screening, participants will provide a DNA sample, which will be analyzed to determine the patient s genotype at several relevant loci. All patients will then complete an eight-week period of citalopram treatment, during which time they will be evaluated bi-weekly with self-report questionnaires and clinician ratings to determine change of MDD symptoms. Participants will also undergo pre- and post-treatment MRS scans to determine glutamate concentration in the prefrontal brain.

Treatment outcome measures:

The Quick Inventory of Depressive Symptomatology - Clinician-Rated (QIDS-C16) will be the primary clinical outcome measure and will be collected at baseline and at each treatment visit. Additionally, levels of glutamate in the prefrontal regions of the brain will be measured by MRS. Clinical response will be defined as a decrease of 50 percent or greater in QIDS-C16 score from baseline, and remission will be defined as a QIDS-C16 score of less than 6.

This proposal is part of a K99 training grant and has undergone extensive external review (K99MH085098-01A2).

  Eligibility

Ages Eligible for Study:   25 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Male and female subjects aged between 25 and 55 years
  • Score of 18 or higher on the 17-item Hamilton Depression Rating Scale (HDRS17). We have set the HDRS17 cutoff score to greater than or equal to18 to increase the contrast signals between remitters and non-remitters, MRS imaging and genotypic groups.
  • Meets DSM-IV criteria for chronic or recurrent non-psychotic MDD
  • No more than 3 failed FDA-approved antidepressant treatments within the current episode
  • No alcohol use in the last 7 days
  • Fluent in English or Spanish
  • Capacity to understand the nature of the study and provide informed consent

EXCLUSION CRITERIA:

  • Lifetime history of schizophrenia, schizoaffective disorder or psychosis not otherwise specified
  • Lifetime history of bipolar disorder (I, II, or not otherwise specified)
  • Lifetime history of anorexia nervosa or bulimia nervosa
  • Current primary obsessive-compulsive disorder (OCD)
  • History of intolerability to citalopram
  • Lack of response to an adequate trial of citalopram or escitalopram in the current or previous episodes of MDD
  • Have failed to respond to more than three antidepressants during current major depressive episode
  • Lack of response to 7 or more sessions of ECT in the current or previous episodes of MDD
  • Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
  • Females who are sexually active and who are not willing to use effective contraception for 8-weeks while participating in this study or are pregnant or breast feeding
  • Concomitant medication use which contraindicates the use of the study medication
  • Requires any of the following exclusionary medications: antipsychotic medications, anticonvulsant medications, antidepressant medications, mood stabilizers, central nervous system stimulants
  • Patients on thyroid medication for hypothyroidism: stable on thyroid medication for < 2 months
  • Current participation in any modality of psychotherapy and the patient is not willing to forgo it during participation
  • Have a history of drug or alcohol dependence or current abuse within the last 3 months
  • Past history of significant head injury with loss of consciousness for about 24 hours or more
  • Current or past history of seizure disorder
  • Suicidal ideation with plan and/or intent
  • Have received any investigational drug within the last 30 days
  • Metallic (ferromagnetic) implants, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, shrapnel fragments, and possible small metal fragments in the eye
  • Unable to lie flat on back for up to 2 hours
  • Claustrophobia in scanner
  • Positive drug screen
  • HIV-positive.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568684

Sponsors and Collaborators
Investigators
Principal Investigator: Gonzalo Laje, M.D. National Institute of Mental Health (NIMH)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01568684     History of Changes
Other Study ID Numbers: 120099, 12-M-0099
Study First Received: March 30, 2012
Last Updated: March 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Magnetic Resonance Spectroscopy
Depression
Depression Treatment
Major Depression
Unipolar Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Citalopram
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on August 20, 2014