Evaluation of Substance P Neurotransmission in Panic Disorder by PET Imaging of NK1 Receptors With [18F]SPA-RQ - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00088738

Purpose

This study is designed to observe the effects of a panic attack in patients with panic disorders and to demonstrate the involvement of Substance P in panic disorder, and thereby, further our understanding of its role in this illness. We will measure levels of Substance P in the brain by obtaining pictures of the brain using PET and MRI....

Condition	Intervention	Phase
Panic Disorder Healthy	Drug: [18F] SPA-RQ	Phase I

MedlinePlus related topics: Anxiety Panic Disorder

Drug Information available for: Carbon dioxide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Evaluation of Substance P Neurotransmission in Panic Disorder by PET Imaging of NK1 Receptors With [18F] SPA-RQ

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

Estimated Enrollment:	84
Study Start Date:	July 2004
Estimated Study Completion Date:	September 2008

Intervention Details:

N/A

Detailed Description:

The involvement of Substance P (SP) in depression and anxiety has been credibly demonstrated in a recent clinical trial. Although the precise physiological activation mechanism of the SP system is not yet known, the likelihood of exaggerated SP pathway activity in the pathogenesis of anxiety is supported in numerous animal studies that illustrate the anxiogenic, and anxiolytic effects of SP and SP antagonists (SPAs), respectively. Studies have further shown that SP release occurs in response to noxious, or aversive stimulation. SP stimulates NK1 receptors that then undergo endocytosis (i.e., internalization) resulting in a decrease in number of NK1 receptors on the cell surface. NK1 receptor quantification before, and after an aversive event, provides a dynamic measurement of SP neurotransmission.

In this protocol, we will use a new PET ligand that has demonstrated ability to serve as an NK1 receptor antagonist, [18F]SPA-RQ ( [18F]-labeled Substance P Antagonist Receptor Quantifier). Using this tracer, we will: 1.) quantify NK1 binding parameters and determine the reliability and reproducibility of these measures in 10 healthy controls, 2.) we will look for regional differences in NK1 receptor binding in 10 patients with panic disorder (PD) versus 10 normal controls, and 3.) We will perform a single-blind, placebo-controlled study to evaluate NK1 receptor binding in PD patients and controls following either saline or doxapram infusion, which is a respiratory stimulant, in 20 patients with panic disorder (PD) versus 20 normal controls. Doxapram acts on both peripheral and medullary chemoreceptors to increase the rate and depth of breathing. It appears to be a potent and specific panicogenic agent, triggering panic attacks. The majority of PD patients, but not controls, are expected to experience a panic attack (aversive event) following the doxapram infusion. Comparison of pre-panic and post-panic NK1 receptor binding in PD patients will provide an estimate of SP release. The goal of the present study is to demonstrate the involvement of SP in panic disorder, and thereby, further our understanding of its role in the psychopathology of this illness.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA: (Phase 1) Whole Body Imaging
Healthy Adults ages 18-50

EXCLUSION CRITERIA (Phase 1) Whole Body Imaging

History of psychiatric disease, substance dependence or traumatic brain injury, severe systemic disease, poor vision or hearing
History of substance abuse within 6 months
Abnormal laboratory tests, including HIV test
Any prior participation in other research protocols involving radiation exposure within the past year
Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits. Limits: A total effective dose 2.5 rem in a year and 2.5 rad per year to the lens of the eyes, gonads and blood-forming organs; and 7.5 rad annually for all other organs.
Pregnancy and Breast Feeding.
Positive HIV test

INCLUSION CRITERIA: (Phase 2) Kinetic

Ages 18-50
Male or Female
Informed consent given
Subjects who regularly consume caffeinated beverages.

EXCLUSION CRITERIA: (Phase 2) Kinetic

DSM-IV Axis I diagnostic criteria such as history of, or current Dx ADHD, mood/anxiety disorder, alcohol or psychoactive substance abuse/dependence
Psychotropic medication or other drugs that may cross the blood brain barrier
Traumatic brain injury, severe systemic disease
Abnormal MRI other than minor atrophy
Abnormal laboratory tests, including HIV test
Claustrophobia
Pregnancy or breast feeding
Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits. Limits: A total effective dose or 5.0 rem in a year
Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the eye, etc.)
Single radial and ulnar arterial circulation
Individuals who recently donated blood
Unable to lay on one's back for PET/MRI scans
Novocaine allergy
Positive HIV test

INCLUSION CRITERIA: (Phase 3A) Challenge

For Patients:

Ages 18-65.
DSM IV criteria for Panic Disorder
Informed consent given.
Subjects who regularly consume caffeinated beverages.

For Controls:

Ages 18-65.
Informed consent given.
Subjects who regularly consume caffeinated beverages.

EXCLUSION CRITERIA: (Phase 3A) Challenge

For Patients and Controls:

Current diagnosis of substance abuse or dependence
History of substance dependence
Psychotropic medication in last 3 weeks (8 weeks for fluoxetine/Prozac) except for benzodiazepene during PET or MRI scans
Abnormal MRI other than minor atrophy
Abnormal laboratory tests, including HIV test
Pulmonary disease (e.g. COPD, asthma)
Claustrophobia
History of hypertension, coronary artery disease and subjects who are taking sympathomimetic medications
Pregnancy or breastfeeding
Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits. Limits: A total effective dose or 5.0 rem in a year
Unable to lay on one's back for PET/MRI scans
Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the eye, etc.)

INCLUSION CRITERIA: (Phase 3B) Comparative

For Patients:

Ages 18-65.
DSM IV criteria for Panic Disorder
Informed consent given.
Subjects who regularly consume caffeinated beverages.

For Controls:

Ages 18-65.
Informed consent given.
Subjects who regularly consume caffeinated beverages.

EXCLUSION CRITERIA: (Phase 3B) Comparative

For Patients and Controls:

Current diagnosis of substance abuse or dependence
History of substance dependence
Psychotropic medication in last 3 weeks (8 weeks for fluoxetine/Prozac) except for benzodiazepene during PET or MRI scans
Abnormal MRI other than minor atrophy
Abnormal laboratory tests, including HIV test
Pulmonary disease (e.g. COPD)
Claustrophobia
History of hypertension, coronary artery disease and subjects who are taking sympathomimetic medications
Pregnancy or breastfeeding
Prior participation in other research protocols within the past year such that a radiation exposure together with the present study would exceed the annual limits. Limits: A total effective dose or 5.0 rem in a year
Unable to lay on one's back for PET/MRI scans
Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the eye, etc.)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00088738

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

Publications:

Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Rupniak NM, et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science. 1998 Sep 11;281(5383):1640-5.

Stockmeier CA, Shi X, Konick L, Overholser JC, Jurjus G, Meltzer HY, Friedman L, Blier P, Rajkowska G. Neurokinin-1 receptors are decreased in major depressive disorder. Neuroreport. 2002 Jul 2;13(9):1223-7.

Deguchi K, Antalffy BA, Twohill LJ, Chakraborty S, Glaze DG, Armstrong DD. Substance P immunoreactivity in Rett syndrome. Pediatr Neurol. 2000 Apr;22(4):259-66.

Study ID Numbers:	040189, 04-M-0189
Study First Received:	July 30, 2004
Last Updated:	September 11, 2008
ClinicalTrials.gov Identifier:	NCT00088738
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Tachykinin
Anxiety
Neuroreceptor
Internalization

Carbon Dioxide
Healthy Volunteer
HV
Panic Disorder

Study placed in the following topic categories:

Panic Disorder
Anxiety Disorders
Mental Disorders
Healthy
Substance P

Additional relevant MeSH terms:

Pathologic Processes
Disease

ClinicalTrials.gov processed this record on January 30, 2009