SPECT Imaging of Alpha 4 Beta 2 Nicotinic Acetylcholine Receptors Using [(123)I]5-I-A-85380 in Schizophrenia
Imaging of Brain Receptors in Healthy Volunteers and in Patients With Schizophrenia
Sponsors
Source
National Institutes of Health Clinical Center (CC)
Brief Summary
This study will use single photon emission computed tomography (SPECT) to study brain
nicotine receptors (proteins on the surface of brain cells) in healthy subjects and in
patients with schizophrenia. Autopsy findings in patients with schizophrenia show changes in
their nicotine receptors. This study will use SPECT to look at these receptors in living
schizophrenia patients and compare them with those in healthy subjects.
The following individuals between 21 and 50 years of age (or between 21 and 80 years of age
for Group 1 only) are eligible for this study: healthy non-smokers (Group 1); schizophrenia
patients who smoke (Group 2); schizophrenia patients who do not smoke (Group 3); healthy
smokers (Group 4); healthy non-smokers (Group 5). Patients with schizophrenia must be taking
olanzapine (Zyprexa) or risperidone (Risperdal) for at least 6 months. All candidates will be
screened at the first visit. Group 1 participants will have three more visits; Groups 2
through 5 will have two more visits.
Visit 1
All participants will be screened with physical and neurological examinations; blood and
urine tests; and neuropsychological tests to assess their ability to learn and remember words
and numbers, to pay attention, and to quickly perform motor tasks, such as putting pegs into
a piece of wood. In addition, they will have an eye movement test and event-related potential
testing. For the eye test, the subject sits in a chair and leans forward with the chin on a
chin rest. A band is tied around the head and very small amounts of invisible (infrared)
light are shined into the eyes. The light is reflected back and measured. Wire electrodes are
placed around the area of the eye and cheek to monitor eye blinks and eye movements. Subjects
are asked to follow a light with their eyes and to look away from a light. For event- related
potential testing, electrodes are placed on the scalp, forehead and cheeks, and brain
activity is recorded while the subject identifies particular pictures and sounds.
Visit 2 (and Visit 3 for Group 1)
Participants will have a SPECT scan. On the night before the scan, the day of the scan, and
for 4 days after the scan, subject take an oral dose of potassium iodide to protect the
thyroid gland from the radioactive tracer used in the SPECT procedure. (Individuals allergic
to potassium iodide will take potassium perchlorate instead.) For the SPECT scan, small
radioactive markers containing 99mTc are glued to the subject's head. Two catheters (thin,
flexible tubes) are placed in veins in the arms to inject the radioactive tracer
[123I]5-I-A-85380 and to draw blood samples. During the scan, the subject lies on a bed with
his or her head held still with a headholder. The scans are taken over a 9-hour period after
injection of the tracer injection. An electrocardiogram, respiration, and blood pressure
measures are taken before injection of [123I]5-I-A-85380, then 5 minutes after the injection,
and again 30 to 60 minutes after the injection. Breath samples are collected every 60
minutes. Blood and urine samples are collected 5 to 6 hours after starting the scan. Group 1
subjects will have a second SPECT scan within 4 weeks of the first.
Visit 3 (Visit 4 for Group 1)
Participants will have a magnetic resonance imaging (MRI) scan. For this procedure, the
subject lies on a table that slides into a narrow metal cylinder with a strong magnetic field
for the scan. The scanner uses a magnetic field and radio waves to produce images that show
structural and chemical changes in tissues. The test lasts up to 1 hour.
Detailed Description
Abnormalities of nicotinic acetylcholine system in schizophrenia are implied by the high
prevalence of cigarette smoking. Because animal and human studies have shown that nicotinic
acetylcholine receptors (nAChRs) play an important role in cognitive function, cognitive
deficits in schizophrenia also suggest abnormalities in these receptors. Postmortem studies
showed abnormalities in high affinity nAChRs in these patients but the direction of the
abnormalities (increase or decrease) were not consistent probably because it is difficult to
control the effects of cigarette smoking and neuroleptics in such studies. In vivo imaging
studies are necessary to study relationship between nAChRs and psychiatric symptoms including
cognitive impairments.
We plan to use a new single photon emission computed tomography (SPECT) tracer,
[(123)I]5-I-A-85380, which appears suitable for imaging the high affinity Alpha 4 Beta 2
subtype of nAChRs. We plan to compare four groups, 1) schizophrenia smokers, 2) schizophrenia
non-smokers, 3) healthy smokers, and 4) healthy non-smokers. All patients will be on stable
doses of olanzapine or risperidone. In addition to comparing [(123)I]5-I-A-85380 binding
among these groups, relationship will be studied between psychiatric symptoms or cognitive
dysfunction and the SPECT measurement of the receptors. Further, to study the reliability of
the SPECT measurement, a test retest study will be preformed in healthy subjects with a wide
range. The proposed study will explore the roles of nAChRs in the psychiatric symptoms,
particularly the cognitive deficits in schizophrenia, which is the central impairment of this
disorder. New findings in this research will lead to enhanced treatment of the cognitive
deficits.
Overall Status
Completed
Start Date
2003-02-01
Completion Date
2004-08-01
Primary Completion Date
N/A
Phase
Phase 2
Study Type
Interventional
Enrollment
100
Condition
Intervention
Eligibility
Criteria
INCLUSION CRITERIA:
Controls-Group 1:
Healthy Diagnosis;
21-80 years;
No Cigarette Smoking;
Plasma Cotinine less than 3 ng/mL;
No olanzapine or risperidone
Smoker Patients-Group 2:
Diagnosis of Schizophrenia;
21-50 years;
Cigarette Smoking greater than 20 per day and greater than 5 years;
Plasma Cotinine greater than 100 ng/mL;
Olanzapine or risperidone greater than 6 mo. and same dose for 2 weeks
Non-Smoker Patients-Group 3:
Diagnosis of Schizophrenia;
21-50 years;
No Cigarette Smoking;
Plasma Cotinine less than 3 ng/mL;
Olanzapine or risperidone greater than 6 mo. and same dose for 2 weeks
Smoker Controls-Group 4:
Healthy Diagnosis;
21-50 years;
Cigarette Smoking greater than 20 per day and greater than 5 years;
Plasma Cotinine greater than 100 ng/mL;
No olanzapine or risperidone
Non-Smoker Controls-Group 5:
Healthy Diagnosis;
21-50 years;
No Cigarette Smoking;
Plasma Cotinine less than 3 ng/mL;
No olanzapine or risperidone
Gender
All
Minimum Age
N/A
Maximum Age
N/A
Healthy Volunteers
Accepts Healthy Volunteers
Location
Facility |
|
National Institute of Mental Health (NIMH) Bethesda Maryland 20892 United States |
Location Countries
Country
United States
Verification Date
2004-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
03-M-0003
Intervention Browse
Mesh Term
Acetylcholine
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Primary Purpose
Treatment
Study First Submitted
June 4, 2003
Study First Submitted Qc
June 3, 2003
Study First Posted
June 4, 2003
Last Update Submitted
March 3, 2008
Last Update Submitted Qc
March 3, 2008
Last Update Posted
March 4, 2008
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.