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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00088738
First received: July 30, 2004
Last updated: September 11, 2008
Last verified: September 2008
  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 1

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

Resource links provided by NLM:


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:
    Drug: [18F] SPA-RQ
    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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00088738     History of Changes
Other Study ID Numbers: 040189, 04-M-0189
Study First Received: July 30, 2004
Last Updated: September 11, 2008
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

Additional relevant MeSH terms:
Panic Disorder
Anxiety Disorders
Mental Disorders
Substance P
(2-fluoromethoxy-5-(5-trifluoromethyltetrazol-1-yl)benzyl)(2-phenylpiperidin-3-yl)amine
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Neurokinin-1 Receptor Antagonists

ClinicalTrials.gov processed this record on August 01, 2014