Assessment of the Effect of Sertaline on the Specific Binding of 123-I MZINT in Healthy Subjects (mZINT)

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.

Study Overview

• Status: Terminated
• Conditions: Depression
• Intervention / Treatment: Drug: 123-I MZINT injection and SPECT imaging

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Access [123I]MZINT and SPECT Imaging

Drug: 123-I MZINT injection and SPECT imaging; SPECT imaging uses the single photon emissions from radioactive compounds that are (most commonly) injected into a patient and are metabolized by specific organs or body systems. SPECT imaging is performed by using a gamma camera to acquire multiple 2-D images (also called projections), from multiple angles. A computer is then used to apply a tomographic reconstruction algorithm to the multiple projections, yielding a 3-D dataset. This dataset may then be manipulated to show thin slices along any chosen axis of the body, similar to those obtained from other tomographic techniques, such as MRI, CT, and PET. The resulting SPECT images reflect body/organ function as opposed to specific anatomy of other imaging modalities such as CT or MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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?	14 DAYS

Secondary Outcome Measures

Outcome Measure	Time Frame
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?	14 DAYS

Collaborators and Investigators

• Sponsor: Institute for Neurodegenerative Disorders
• Collaborators: Molecular NeuroImaging
• Investigators: Principal Investigator: Danna L. Jennings, MD, Unafilliated

Publications and helpful links

General Publications

• 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.

Helpful Links

• IND web page

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: May 4, 2007
• First Submitted That Met QC Criteria: May 7, 2007
• First Posted (Estimate): May 8, 2007

Study Record Updates

• Last Update Posted (Actual): April 3, 2019
• Last Update Submitted That Met QC Criteria: April 1, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Dopamine; Neurological
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: mZINT_003