Clinical trial NCT00470925: Assessment of the Effect of Sertaline on the Specific Binding of 123-I MZINT in Healthy Subjects
Official title: Assessment of the Effect of Sertaline on the Specific Binding of 123-I MZINT in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Depression
Keywords: Neurological
Dopamine
Lead sponsor: Institute for Neurodegenerative Disorders
Sponsor class: OTHER
Collaborators: name: Molecular NeuroImaging
First posted: 2007-05-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The overall purpose of this project is to evaluate the effect of sertraline administration on the binding of 123-I mZINT in 10 healthy subjects. All study procedures will be conducted at the Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging (MNI) in New Haven, CT.

Detailed description: Serotonin (5-HT) is a monoamine neurotransmitter found in the peripheral and central nervous system. It is responsible for regulating a wide variety of physiological processes and higher CNS functions. 5-HT neurons project diffusely throughout the brain, innervating the cerebral cortex, hippocampus, thalamus, midbrain, brainstem and cerebellum, and play a prominent role in regulating physiological and behavioral responses such as arousal, thermoregulation, anxiety, and affect.

All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, and a baseline physical and neurological evaluation. healthy subjects will undergo a baseline 123-I MZINT injection and SPECT imaging described below. At baseline, healthy subjects will be started on either no treatment (n=4), or one of three different doses of sertraline (25 mg/day n=2, 50 mg/day n=2 or 150 mg/day n=2), which will be administered over a 14 day period. Fourteen days following imaging session 1, all subjects (treated with sertraline and untreated) will undergo a second 123-I MZINT and SPECT imaging study. Data from the baseline and follow-up SPECT images will be compared to evaluate for any effect of sertraline on regional brain uptake of 123-I MZINT. The subjects that are randomized to no treatment will serve as controls and provide preliminary test-retest reproducibility data on the imaging outcome measure.

The goal of this proposal is to evaluate the effect of sertraline administration on the specific \[123-I\] mZINT. In vitro and in vivo data from early human studies and baboon studies strongly support further evaluation of \[123I\] mZINT in healthy subjects.

Eligibility criteria: Inclusion Criteria:

* The subject is aged 18-70.
* Written informed consent is obtained.
* The participant has no clinically significant clinical laboratory value and/or clinically significant unstable medical, neurological or psychiatric illness.
* For females, non-child bearing potential or negative urine pregnancy test on day of \[123I\] mZINT injection.
* Willingness to comply with the study protocol

Exclusion Criteria:

* The subject has a clinically significant clinical laboratory values abnormality, and/or medical or psychiatric illness.
* The subject has any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
* The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
* Use of all prescription drugs or non-prescriptions drugs that may effect serotonin such as antidepressants including sertraline, fluoxetine, fluvoxamine, venlafaxine within 60 days of baseline imaging study.
* The participant has a history of alcohol, narcotic, or any other drug abuse as defined by the Diagnostic and Statistical Manual of the American Psychiatric Association, 4th Edition (DSM IV) {American Psychiatric Association, 1994 #2} within the past 2 years.
* Pregnancy

Primary outcomes:
measure: Does administration of sertraline have an effect on the specific binding of 123-mZINT in healthy subjects evaluated with serial, dynamic SPECT imaging at baseline and after 14 days of sertraline treatment?
timeFrame: 14 DAYS
Secondary outcomes:
measure: Is there a dose effect of sertraline on 123I MZINT binding? Do higher doses of sertraline have a more profound effect on the specific binding of 123I MZINT than lower doses of sertraline?
timeFrame: 14 DAYS
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
Study officials:
affiliation: unafilliated
name: Danna L. Jennings, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brooks DJ, Piccini P. Imaging in Parkinson's disease: the role of monoamines in behavior. Biol Psychiatry. 2006 May 15;59(10):908-18. doi: 10.1016/j.biopsych.2005.12.017. Epub 2006 Apr 11.