Protocol Number: 04-M-0189

Title:

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

Number:

04-M-0189

Summary:

Researchers believe the brain releases a chemical called "Substance P" in response to unpleasant and threatening situations, causing some people to experience panic disorder. To investigate this possibility, researchers will use a radioactive tracer called [18F]SPA-RQ, which will permit them to observe brain activity through a positron emission tomography (PET) scan and estimate how much Substance P has been released. Approximately 44 volunteers aged 18 - 65 will participate in the three phases of this study.

Each phase will begin with a medical screening that includes a physical exam, blood tests, a mental health questionnaire or evaluation, and an EKG. Routine medical monitoring and tests will occur throughout the study and after each PET scan. All PET scans in this study will be preceded first by a short transmission scan to help understand later scans, and then by an injection of the radioactive tracer (through a catheter in an arm vein).

The first phase will investigate the best use of the tracer. Twelve healthy volunteers will undergo PET scans requiring about 6 hours. Volunteers will return the next day to give blood and urine samples.

The second phase will investigate the accuracy of the researchers' measurements. Twelve healthy volunteers will undergo PET scans requiring about 4 hours. A second set of PET scans will occur within a week of the first set. During this phase, volunteers will also make a separate visit for an MRI scan requiring about 1 hour.

The third phase will include 20 volunteers with panic disorder, and 20 normal volunteers who will act as controls. Researchers will give volunteers a breathing test involving either normal room air, or air with a higher-than-usual content of carbon dioxide (CO2). Researchers expect the CO2 to induce panic attacks in volunteers with panic disorder. Volunteers will then undergo PET scans requiring about 4 hours. A second set of PET scans will occur within a week of the first set. Researchers will compare PET scans from before and after the panic attacks to estimate the amount of Substance P released. During this phase, volunteers will also make a separate visit for an MRI scan requiring about 1 hour and will give blood samples for use in DNA research.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility 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

-Pregnancy and Breast Feeding

-Positive HIV test

INCLUSION CRITERIA: (Phase 2) Kinetic

-Ages 18-50

-Male or Female

-Informed Consent given

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

-Pregnancy or breastfeeding

-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

-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 CRITERI: (Phase 3) Challenge

For Patients:

-Ages 18-65.

-DSM IV criteria for Panic Disorder

-Informed consent given.

For Controls:

-Ages 18-65.

-Informed consent given.

EXCLUSION CRITERIA: (Phase 3) Challenge-Patients and Controls

-DSM-IV Axis I diagnostic criteria other than Panic Disorder

-DSM-IV criteria for psychoactive substance abuse/dependence

-Psychotropic medication in last 3 weeks (8 weeks for fluoxetine/Prozac) or current use of other drugs that may cross the blood brain barrier

-Abnormal MRI other than minor atrophy

-Abnormal laboratory tests, including HIV test

-Pulmonary disease (e.g. COPD, asthma)

-Migraine headaches

-Claustrophobia

-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

-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.)

Special Instructions: Currently Not Provided

Keywords:

Tachykinin

Anxiety

Neuroreceptor

Internalization

Carbon Dioxide

Recruitment Keywords:

Healthy Volunteer

HV

Panic Disorder

Conditions:

Panic Disorder

Investigational Drug(s):

[18F] SPA-RQ

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

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.

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