PharmacofMRI of Anxiolytic Medications (Pregabalin)

The purpose of this study is to use functional magnetic resonance imaging (fMRI) in healthy controls to examine the acute effects of certain anxiolytic medications on brain function. In this case, the medication pregabalin will be used. The investigators hypothesize that pregabalin (at doses of 50 mg and 200 mg, versus placebo) will yield a reduction in amygdala and insula activity (in a dose-dependent fashion) during emotion processing using fMRI.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders
• Intervention / Treatment: Drug: Pregabalin 50mg; Drug: Pregabalin 200 MG; Drug: placebo

Detailed Description

Increased amygdala and insula activity have been implicated in neurobiological models of anxiety. Using fMRI, the anxiolytic medication, lorazepam, has previously been found to decrease activation in these areas during the processing of emotional stimuli. This study aims to replicate those results but by using a different medication, pregabalin. An eventual aim of this study, in combination with future studies, is to evaluate the utility of fMRI as a tool to identify anxiolytic function in both established and novel compounds that may be used to treat anxiety.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male, or female (not pregnant or intending to become pregnant during the study)
• Between the ages of 18-30.
• In good general health.
• No specific contraindications to the drug being administered

Exclusion Criteria:

• Subjects with a history of DSM-IV depressive disorder, psychotic disorder, anxiety disorder
• Subjects who meet criteria for substance abuse or dependence within the last 6 months
• Subjects with an positive urine screen for illicit drugs having clinically significant abnormal laboratory, ECG or physical examination findings not resolved by the baseline visit
• Patients who have taken psychotropic drugs or antidepressants (including monoamine oxidase inhibitors, MAOI's) within the last year
• Subjects who are left-handed.
• Subjects suffering suffers from claustrophobia, or phobia for injections or blood
• Magnetic Resonance Imaging related exclusion criteria: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), subjects who have ever been a metal worker/welder; history of eye surgery/eyes washed out because of metal, aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, subjects who are in the first trimester of pregnancy, subjects with an I.U.D. (birth control device), a shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; One dose of matched oral placebo to be administered one hour prior to fMRI scan
Active Comparator: Pregabalin 50 mg; Pregabalin oral tablets (50 mg)	Drug: Pregabalin 50mg; One dose of oral pregabalin (50 mg) to be administered one hour prior to fMRI scan; Other Names: Lyrica
Active Comparator: Pregabalin 200 mg; Pregabalin oral tablets (200 mg)	Drug: Pregabalin 200 MG; One dose of oral pregabalin (200 mg) to be administered one hour prior to fMRI scan; Other Names: Lyrica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Pregabalin (Two Doses) Versus Placebo	Region of Interest (ROI) analysis of contrast of doses (high and low) of pregabalin vs placebo on brain activity at rest and during emotional stimuli using fMRI and clinical scales.	Week 1, 2, 3 (Cross-over Design)

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: National Institute of Mental Health (NIMH)

Publications and helpful links

General Publications

• Aupperle RL, Ravindran L, Tankersley D, Flagan T, Stein NR, Simmons AN, Stein MB, Paulus MP. Pregabalin influences insula and amygdala activation during anticipation of emotional images. Neuropsychopharmacology. 2011 Jun;36(7):1466-77. doi: 10.1038/npp.2011.32. Epub 2011 Mar 23.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 26, 2008
• First Submitted That Met QC Criteria: June 27, 2008
• First Posted (Estimate): June 30, 2008

Study Record Updates

• Last Update Posted (Actual): April 9, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: functional magnetic resonance imaging; anxiety; fMRI; pregabalin; Lyrica
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: UCSD IRB 060407 - B; R01MH075792 (U.S. NIH Grant/Contract)