The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects (GuaKet)

This study has suspended participant recruitment.
(We are seeking additional funds to continue.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
John H. Krystal, Yale University
ClinicalTrials.gov Identifier:
NCT01600885
First received: May 15, 2012
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

The purpose of the study is

  1. To establish the feasibility of fMRI studies of the interaction of guanfacine and ketamine.
  2. To explore the possibility that guanfacine can ameliorate the negative effects of ketamine on task-related prefrontal activation.
  3. To assess the strength of any interaction between guanfacine and ketamine.

Condition Intervention
Normal NMDA Receptor Function
Drug: Guanfacine then Placebo
Drug: Placebo then Guanfacine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Functional magnetic resonance imaging [ Time Frame: Within 4 hours of dose administration ] [ Designated as safety issue: No ]
    Scans will be analyzed for task-related prefrontal activation


Secondary Outcome Measures:
  • Task performance [ Time Frame: Within 4 hours of dose administration ] [ Designated as safety issue: No ]
    During the fMRI scans, subjects will be asked to complete a spatial task that utilizes Working Memory.


Estimated Enrollment: 20
Study Start Date: August 2008
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Guanfacine then Placebo
During the first study session, the participant will receive guanfacine before undergoing a ketamine-infusion fMRI. During the second study session, at least two weeks later, the participant will receive a placebo before undergoing a ketamine-infusion fMRI.
Drug: Guanfacine then Placebo

During the first study session, the patient will be given 3mg of guanfacine before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) will be given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant will receive a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation will be measured during a spatial working memory task. The entire scan will last approximately two and a half hours and the ketamine infusion will be up to one hour and 15 minutes.

The second study session will be identical except that the patient will be given a placebo instead of the guanfacine.

Active Comparator: Placebo then Guanfacine
During the first study session, the participant will receive a placebo before undergoing a ketamine-infusion fMRI. During the second study session, at least two weeks later, the participant will receive guanfacine before undergoing a ketamine-infusion fMRI.
Drug: Placebo then Guanfacine

During the first study session, the patient will be given a placebo before the fMRI scan. Then when in the scanner, a bolus of ketamine (0.23mg/kg over 1 min) will be given during the visual fixation scan. Immediately after completion of the 1 min bolus, the participant will receive a steady state ketamine infusion of 0.58 mg/kg/hour and brain activation will be measured during a spatial working memory task. The entire scan will last approximately two and a half hours and the ketamine infusion will be up to one hour and 15 minutes.

The second study session will be identical except that the patient will be given 3mg of guanfacine instead of the placebo.


Detailed Description:

Potential subjects will be interviewed over the phone and, if appropriate, will be scheduled for a screening session. Participants who meet study criteria will participate in two study sessions separated by at least two weeks. The sessions will be identical except on one day they will receive guanfacine and on the other, they will receive a placebo.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age between 21 and 45, inclusive
  • Right-handed
  • Have at least a 12th grade education level or equivalent
  • Able to read and write English as a primary language
  • Willing to refrain from caffeine and alcohol use for one week prior to each MRI session.

Exclusion Criteria:

  • Abnormality on physical examination
  • A 12 lead ECG at screening has clinically significant abnormalities as determined by the physician reading the ECG
  • A positive pre-study urine drug screen or, at the study physicians' discretion on any drug screens given before the scans
  • Abnormality on clinical chemistry or hematology examination at the pre-study medical screening.
  • History of positive HIV or Hepatitis B.
  • Has received either prescribed or over-the-counter (OTC) centrally active medicine or herbal supplements within the week prior to the MRI scan.
  • History of any substance abuse disorder meeting DSM-IV criteria with the exception of nicotine
  • Any history of DSM-IV Axis I psychiatric disorders,
  • Any history of major medical or neurological disorders
  • Any history indicating learning disability, mental retardation, or attention deficit disorder.
  • First-degree relative with Axis I DSM-IV disorder including substance abuse or dependence.
  • Any clinically significant abnormalities on screening electrocardiogram
  • Any history of head injury
  • Any evidence of psychosis-like symptoms, as indicated by elevated scores on the Perceptual Aberration-Magical Ideation (Chapman, Chapman et al. 1978; Eckblad, Chapman et al. 1983) and the revised Social Anhedonia scales(Eckblad, Chapman et al. unpublished)
  • A positive urine toxicology screen for illicit substance use or positive alcohol breathalyzer test conducted at screening interview and prior to each MRI session
  • Known sensitivity to ketamine.
  • Body circumference of 52 inches or greater.
  • History of claustrophobia
  • Any clinically significant impairment of color vision or visual acuity after correction available in the scanner.
  • Presence of cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening questionnaire
  • Pregnancy or breast-feeding would exclude potential participants and all female subjects will receive a urine pregnancy test at screening and before each MRI scan.
  • Donation of blood in excess of 500 mL within 56 days prior to dosing.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Blood pressure must be higher than 90/70. Pulse must be greater than 40 unless the participant is cleared by a study physician
  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: NCT01600885

Locations
United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06511
Yale Magnetic Resonance Research Center
New Haven, Connecticut, United States, 06520
Veterans Affairs Hospital
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: John H Krystal, M.D. Yale University
Study Director: Naomi R Driesen, Ph.D. Yale University
  More Information

Publications:

Responsible Party: John H. Krystal, Chair, Department of Psychiatry, Yale University
ClinicalTrials.gov Identifier: NCT01600885     History of Changes
Other Study ID Numbers: 0807004092
Study First Received: May 15, 2012
Last Updated: May 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
Guanfacine
Ketamine
Functional Magnetic Resonance Imaging
Prefrontal Cortex Activity
Receptors, N-Methyl-D-Aspartate
Receptors, Adrenergic, alpha-2
Memory, Short-Term
Schizophrenia

Additional relevant MeSH terms:
Ketamine
Guanfacine
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antihypertensive Agents
Cardiovascular Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on July 24, 2014