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p11 Protein Levels in Patients With Major Depressive Disorder Treated With Citalopram

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00697268
First received: June 12, 2008
Last updated: November 11, 2014
Last verified: September 2014
  Purpose

This study will compare levels of p11 protein in people with and without major depressive disorder (MDD) and examine if p11 levels in patients are affected by treatment with citalopram (Celexa).

Healthy normal volunteers and patients with chronic or recurrent major depression between 18 and 65 years of age may be eligible for this study.

Participants undergo the following tests and procedures:

Healthy Volunteers

  • Psychiatric interview and medical examination, questions about family history
  • Blood draw

Patients with MDD

Phase 1 - Evaluation and Discontinuation of Medications

  • Physical examination, electrocardiogram, blood tests
  • Gradual antidepressant medication withdrawal, followed by 2- to 6-week drug-free period. If needed, medicines for anxiety and difficulty sleeping may be prescribed.

Phase 2 Citalopram Treatment

  • Start daily citalopram treatment
  • Evaluations at the start of phase 2 and every week for 8 weeks with following procedures:
  • Symptoms ratings interview and questionnaires
  • Review of side effects and new medications
  • Blood pressure and pulse measurements
  • Blood and urine tests

At the end of the study, plans are developed for long-term treatment and transfer of care to the patient s own physician.


Condition
Depression

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: An Investigation to Determine Whether Levels of P11 Protein in Peripheral Blood Cells Correlate With Treatment Response to Citalopram in Patients With Major Depressive Disorder

Resource links provided by NLM:


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

Primary Outcome Measures:
  • We will study whether blood cell levels of p11 differ between healthy individuals and patients with depression. Moreover, we will study whether the levels of p11 are affected by treatment with the selective serotonin reuptake inhibitor, citalopr...

Secondary Outcome Measures:
  • Complementary work will continue at other laboratories to better characterize the role of p11 in the pathophysiology of depression (e.g., animal studies, post-mortem studies).

Estimated Enrollment: 146
Study Start Date: June 2008
Detailed Description:

Major depressive disorder (MDD) is a serious, debilitating, life-shortening illness that affects many persons of all ages and backgrounds. While treatments are effective for a significant portion of patients with MDD, progress in developing more effective treatments is lagging. Furthermore, with regards to existing antidepressant medications, there are yet no reliable predictors of the likelihood of remission, response or non-response with an initial trial of an antidepressant medication. Identifying factors that are likely to predict response would have the advantage of personalizing treatment to a particular individual; that is selecting the antidepressant medication that is most likely to give the greatest probability of having a favorable outcome.

The serotonin system has been implicated in the pathophysiology of depression and mechanism of action of existing effective antidepressant treatments. Fourteen different serotonin receptors have been identified to date. One of them, 5-HT1B, plays an important role in regulating serotonin neurotransmission. Recently, p11 (a member of the S100 family of proteins) was found to interact with 5-HT1B receptors (Svenningsson et al 2006; Svenningsson and Greengard 2007). p11 mRNA levels are markedly reduced in the forebrain in helpless H/Rouen mice and the level of p11 mRNA was down-regulated in the anterior cingulate cortex from depressed patients. p11 mRNA is distributed in an anatomical pattern that closely resembled that of 5-HT1B receptor mRNA, including cortex, hippocampus, hypothalamus and raphe nuclei. Chronic administration of the antidepressants imipramine, tranylcypromine, and citalopram significantly increase the level of p11 in cortex. Finally, we have found that chronic treatment with fluoxetine increases p11 in peripheral mononuclear cells in monkeys.

We will now study whether the blood cell levels of p11 differ between healthy individuals and patients suffering from unipolar depression. Moreover, we will study whether the levels of p11 are affected by treatment with the selective serotonin reuptake inhibitor, citalopram. Complementary work will continue at other laboratories to better characterize the role of p11 in the pathophysiology of depression (e.g., animal studies, post-mortem studies).

In addition, we will also acquire a battery of magnetic resonance imaging (MRI) scans in a subset of 45 more homogeneous depressed subjects, and 45 matched healthy controls at baseline and at 8 weeks. There is a growing body of evidence implicating morphometric and physiologic abnormalities, measureable by MRI, in the pathophysiology of major depressive disorder. We will assess both baseline differences between depressed subjects and healthy controls, treatment effects, and search for possible MRI markers predicting treatment response.

This is an open label study which will be performed at the National Institute of Mental Health. In all, 82 adult subjects with major depressive disorder, between the ages of 18 and 65 years, will be recruited from the community. In addition, we will perform p11 measurements in blood cells from 64 healthy control subjects.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

CRITERIA FOR INCLUSION OF DEPRESSED PATIENTS:

  • age 18-65 years
  • written informed consent completed (consent-incapacitated subjects will not be eligible)
  • score 20 or higher on the Montgomery-Asberg Depression Rating Scale (MADRS)
  • meets DSM-IV criteria for chronic or recurrent nonpsychotic MDD
  • patients who are on non-excluded concomitant medications.
  • no more than 3 failed antidepressant treatments within the current major depressive episode
  • no alcohol use (last 7 days)

ADDITIONAL CRITERIA FOR INCLUSION OF DEPRESSED PATIENTS FOR MRI IMAGING:

  • age 18 55 years
  • subjects must have either a family history of mood disorders, or have a history of

multiple major depressive episodes

  • age of onset of depressive symptoms less than 45 years
  • no history of past alcohol or substance dependence (excluding nicotine) or alcohol or substance abuse (excluding nicotine) within the past year.
  • no use of benzodiazepines within 2 weeks of either MRI scan

CRITERIA FOR INCLUSION OF HEALTHY CONTROL SUBJECTS:

  • age 18-65 years
  • written informed consent completed
  • no current or past diagnosis of axis I psychiatric disorder (DSM-IVTR)
  • no alcohol use (last 7 days)
  • physically healthy

ADDITIONAL CRITERIA FOR INCLUSION OF HEALTHY CONTROL SUBJECTS FOR MRI IMAGING:

  • age 18 55 years
  • no history of past alcohol or substance dependence (excluding nicotine) or alcohol or substance abuse (excluding nicotine) within the past year.

EXCLUSION CRITERIA:

CRITERIA FOR EXCLUSION OF DEPRESSED PATIENTS:

  • history of bipolar disorder (I, II, or NOS) (lifetime)
  • history of schizophrenia
  • history of schizoaffective disorder or
  • psychosis NOS (lifetime)
  • history of anorexia nervosa or bulimia nervosa (lifetime)
  • current primary obsessive-compulsive disorder (OCD) or current post traumatic stress disorder (PTSD) whose onset preceded the onset of Major Depressive Disorder
  • history of clear-cut intolerability to the study medication
  • lack of response to an adequate trial of the study medication (citalopram) in the current or past episodes of MDD
  • did not respond to 7 or more sessions of ECT in the current episode of MDD
  • Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
  • has general medical condition which contraindicates the use of the study medication
  • is on concomitant medication which contraindicates the use of the study medication
  • requires immediate hospitalization for psychiatric disorder
  • requires antipsychotic medications or mood stabilizers
  • Non-postmenopausal (less than 2 years since last period) females of childbearing potential who are sexually active and who are not using adequate (hormonal, double barrier, surgical) contraception, or who are pregnant or breast feeding
  • patients currently taking any of the exclusionary medications detailed in protocol (including antipsychotic medications, anticonvulsant medications, antidepressant medications, mood stabilizers, central nervous system stimulants) in the 2 weeks prior to Study Period II.
  • patients taking thyroid medication for hypothyroidism may be included if they have been stable on the medication for greater than 3 months
  • patients can participate in a modality of psychotherapy that is not targeting the symptoms of depression (e.g., supportive therapy, marital therapy)
  • therapy that is depression specific, such as Cognitive Therapy (CT) or Interpersonal Psychotherapy of Depression (IPT) is not allowed during participation
  • subjects must be fluent in English and have the capacity to understand the nature of the study and sign the written informed consent.
  • current alcohol dependence or abuse (last 3 months)
  • patient has a prolonged QTc (greater than or equal to 450 msec), as shown on ECG

ADDITIONAL CRITERIA FOR EXCLUSION OF DEPRESSED PATIENTS FOR MRI IMAGING:

  • subjects meeting general exclusion criteria for MRI scanning (e.g. implanted cardiac pacemaker, intraocular metal) will be excluded from the MRI procedures only.
  • subjects with structural lesions visible on MRI will be excluded from further MRI procedures
  • subjects with diabetes or hypertension will be excluded

CRITERIA FOR EXCLUSION OF HEALTHY CONTROL SUBJECTS:

  • subjects currently taking any of the exclusionary medications detailed in protocol in the 2 weeks prior to evaluation
  • current alcohol dependence or abuse (last 3 months)
  • history of major depression or bipolar disorder in any first degree relative

ADDITIONAL CRITERIA FOR EXCLUSION OF HEALTHY CONTROL SUBJECTS:

  • subjects meeting general exclusion criteria for MRI scanning (e.g. implanted cardiac pacemaker, intraocular metal) will be excluded from the MRI procedures only.
  • subjects with structural lesions visible on MRI will be excluded from further MRI procedures
  • subjects with diabetes or hypertension will be excluded
  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: NCT00697268

Contacts
Contact: Libby Jolkovsky (877) 646-3644 libby_jolkovsky@nih.gov
Contact: Carlos A Zarate, M.D. (301) 451-0861 zaratec@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00697268     History of Changes
Other Study ID Numbers: 080150, 08-M-0150
Study First Received: June 12, 2008
Last Updated: November 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Depression
Depression Treatment
Unipolar Depression
Citalopram
Serotonin
Major Depression
Healthy Volunteer
HV

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

ClinicalTrials.gov processed this record on November 25, 2014