Imaging Serotonin 5HT1A Receptors in Patients With Major Depressive Disorder

NCT01313403 | Withdrawn

• 2 other identifiers: 11009711-M-0097
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- Medications to treat major depression act on a brain chemical called serotonin, which binds to receptors on brain cells. More research is needed on how serotonin receptors work in the brain, and imaging studies such as magnetic resonance imaging (MRI) can provide information on how these receptors function in the brains of individuals with depression and healthy volunteers. The experimental radioactive chemical \[11C\]CUMI has been designed to react with serotonin receptors, and researchers are interested in studying its effectiveness using positron emission tomography (PET) scanning to see how well it gets into the brain. Objectives: \- To evaluate the effectiveness of the radiotracer \[11C\]CUMI in brain imaging studies of serotonin receptors. Eligibility: \- Individuals between 18 and 55 years of age who either have been diagnosed with major depressive disorder or are healthy volunteers. Design:

• Participants will be screened with a full medical history, physical and psychiatric examination, blood and urine tests, and questionnaires about mood. Participants will also have an electrocardiogram at this visit.
• At the first study visit, participants will have a MRI scan of the brain to provide baseline data on brain function.
• At the second study visit, participants will have a PET scan with the \[11C\]CUMI contrast agent.
• No treatment will be provided as part of this protocol....

Conditions

Major Depression; Unipolar Depression; Depression; Anxiety Disorder

Keywords

5-HT1A Receptors; Major Depression; PET Imaging; Depression; Healthy Volunteer; HV

Interventions

Antidepressant (SSRI) OTHER

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be between 18-55 years old.
• Subjects must be able and willing to give written informed consent.
• Subjects must have a DSMIV diagnosis of Major Depressive Disorder (MDD).
• Subjects must at the time of study enrollment be experiencing an episode of Major Depression per DSMIV criteria, and as demonstrated by a Hamilton Depression Rating Scale (HDRS; 17 item) greater than 18 (Williams, 1988).
• Subjects must be adults between 18-55 years old.
• Subjects must be able and willing to give written informed consent.
• Hamilton Depression Rating Scale (HDRS-17 item) less than 8.

You may not qualify if:

• With the exception of substance abuse and anxiety disorders, any past or current Axis I diagnosis other than Major Depressive Disorder. With regard to substance abuse disorders, we will allow past diagnoses so long as there is no question of substance or alcohol dependence, the patient has not had substance abuse patterns in the year prior to enrollment, and other criteria regarding LSD and ecstasy use are met (see below). We will screen for substance abuse patterns in the year prior to enrollment by excluding heavy alcohol use, as defined as greater than 14 drinks per week for men and greater than 7 drinks per week for women. With regard to anxiety disorders, we will allow past or present diagnoses of Generalized Anxiety Disorder, social phobia and panic disorder, so long as the anxiety disorder is not felt to outweigh the magnitude of the diagnosis of Major Depressive Disorder. This will be determined by clinical investigators in this protocol. Particular attention will be made to ensure that the patient does not have a diagnosis of Bipolar disorder, Schizoaffective disorder or Premenstrual dysphoric disorder (PMDD).
• Any history of Lysergic acid diethylamide (LSD) use, because it may alter serotonin receptor properties.
• History of ecstasy use more than 3 times in life, because it may alter serotonin receptor properties.
• Current suicidality or serious depressive symptoms warranting more intensive management than weekly visits in our psychiatric outpatient clinic
• Psychiatric symptoms warranting psychotropic medications other than the selected SSRI study drug. The exception to this is infrequent use of benzodiazepine (e.g. lorazepam (Ativan), 0.5-1.0 mg for anxiety). Infrequent is defined here as less often than 3 times per week.
• In women, irregular menses such that it will not be possible to determine the phase of the cycle. This is because previous data show that the phases of the menstrual cycle may affect 5-HT1A binding by radioligand.
• Clinically significant laboratory abnormalities.
• Psychotropic medication use (including benzodiazepines and illicit drugs) during the 21 days (42 days for fluoxetine) prior to the PET scan. The exception would be 1-5 doses of 0.5-1.0mg of benzodiazepine (lorazepam (Ativan)) by mouth, separated by at least 24 hours between doses, for anxiety related to study procedures.
• Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, brain masses or lesions \> 1cm in diameter.
• Positive HIV status.
• Metallic foreign bodies that would be affected by the MRI magnet, or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan.
• Head trauma resulting in a period of unconsciousness lasting longer than 10 minutes.
• History of fetal alcohol syndrome or other neurodevelopmental disorder.
• Recent exposure to radiation (i.e., PET from other research) which when combined with this study would be above the allowable limits.
• Positive urine drug screen.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Related Publications (4)

• Alpert JE, Franznick DA, Hollander SB, Fava M. Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder. J Clin Psychiatry. 2004 Aug;65(8):1069-75.

  PMID: 15323591 BACKGROUND

• Amsterdam JD, Brunswick DJ, Gibertini M. Sustained efficacy of gepirone-IR in major depressive disorder: a double-blind placebo substitution trial. J Psychiatr Res. 2004 May-Jun;38(3):259-65. doi: 10.1016/j.jpsychires.2003.10.005.

  PMID: 15003431 BACKGROUND

• Amsterdam JD. Gepirone, a selective serotonin (5HT1A) partial agonist in the treatment of major depression. Prog Neuropsychopharmacol Biol Psychiatry. 1992 May;16(3):271-80. doi: 10.1016/0278-5846(92)90079-t.

  PMID: 1350353 BACKGROUND

• Artigas F, Romero L, de Montigny C, Blier P. Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists. Trends Neurosci. 1996 Sep;19(9):378-83. doi: 10.1016/S0166-2236(96)10037-0.

  PMID: 8873352 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder; Depression; Anxiety Disorders

Interventions

Antidepressive Agents; Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Study Officials

• Carlos A Zarate, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 11, 2011
• Study Start: February 10, 2011
• Primary Completion: April 25, 2012
• Study Completion: April 25, 2012
• Last Updated: July 2, 2017

Record last verified: 2012-04-25