Evaluation of Substance P Neurotransmission in Panic Disorder by PET Imaging of NK1 Receptors With [18F]SPA-RQ
Summary
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....
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.
Study Design
Primary Purpose: Treatment
Conditions
Panic Disorder
Intervention
[18F] SPA-RQ
Location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892
Status
Completed
Source
National Institutes of Health Clinical Center (CC)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00088738
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Panic Disorder
A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.
Isocarboxazid
An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311)
Tranylcypromine
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
Serotonin Uptake Inhibitors
Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the ADRENERGIC UPTAKE INHIBITORS also inhibit serotonin uptake; they are not included here.
Catatonia
A neuropsychiatric disorder characterized by one or more of the following essential features: immobility, mutism, negativism (active or passive refusal to follow commands), mannerisms, stereotypies, posturing, grimacing, excitement, echolalia, echopraxia, muscular rigidity, and stupor; sometimes punctuated by sudden violent outbursts, panic, or hallucinations. This condition may be associated with psychiatric illnesses (e.g., SCHIZOPHRENIA; MOOD DISORDERS) or organic disorders (NEUROLEPTIC MALIGNANT SYNDROME; ENCEPHALITIS, etc.). (From DSM-IV, 4th ed, 1994; APA, Thesaurus of Psychological Index Terms, 1994)
Clinical Trials
Changes of Cerebral Glucose Metabolism After 12 Weeks of Paroxetine Treatment in Panic Disorder
Panic disorder is one of the most prevalent and disabling psychiatric disorders. Brain regions such as amygdala, hippocampus, periaqueductal gray (PAG), locus coeruleus, parahippocampal g...
The purpose of this study is to assess the impact of three different treatment modalities on panic symptoms, quality of life and use of health services among individuals consulting an emer...
Efficacy of Treatment for Panic Disorder
The purpose of these questionnaires is to give us an overview of how panic has affected your life and perhaps also to give us some clues about things that may have set you up to experience...
Staccato™ Alprazolam for Inhalation in Panic Attack
We are developing Staccato™ Alprazolam for the treatment of Panic attacks associated with panic disorder. This study will provide an initial assessment of efficacy, and to continue to de...
Levetiracetam Treatment of Panic Disorder and Lactate-Induced Panic Attacks
The main purpose of this research study is to determine whether the drug Levetiracetam (Keppra™) is effective in the prevention of panic attacks. The drug Levetiracetam (Keppra™) has b...
PubMed Articles
A possible association between panic disorder and a polymorphism in the preproghrelingene.
The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety dis...
Background: The present study evaluated attentional bias in adolescents diagnosed with panic disorder. Although a large body of research exists in the area of attentional bias in adults, this feature...
OBJECTIVE: The epidemiology of panic disorder has not been investigated in the past in the UK using a nationally representative sample of the population. The aim of the present paper was to examine th...
Caffeine challenge test and panic disorder: a systematic literature review.
This systematic review aimed to examine the results of studies that have investigated the induction of panic attacks and/or the anxiogenic effect of the caffeine challenge test in patients with panic...
We investigated the comorbidity rate of migraine in outpatients with panic disorder, and the efficacy of pharmacotherapy for both disorders. Fifty-four patients who met the Diagnostic and Statistical...
