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Anesthesia and Functional Connectivity: An Analysis of fMRI Changes

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ClinicalTrials.gov Identifier: NCT02196259
Recruitment Status : Terminated (Funding cessation.)
First Posted : July 22, 2014
Results First Posted : May 2, 2017
Last Update Posted : May 2, 2017
Sponsor:
Information provided by (Responsible Party):
Scott Peltier, University of Michigan

Brief Summary:

Functional connectivity is defined as a correlation in neural activity between distinct regions of the brain. Several recent studies have demonstrated areas of low-frequency functional connectivity inherent to brain tissue at rest. These oscillations can be measured using functional magnetic resonance imaging (fMRI) and appear to be synchronized between related areas of the brain.

To date, no investigators have examined the effects of low-dose anesthesia on functional connectivity. This study will image the human brain under conditions of rest, and low-dose anesthetic induced sedation. Quality of the acquired signals will be evaluated and functional networks in the brain will be examined. Of interest is whether administration of a low-dose anesthetic disrupts functional connectivity in the brain, and whether a disruption of functional connectivity is responsible for the reported analgesic and antidepressant effects of a anesthetic.

Participation in the study includes four visits: an in-person interview, an initial fMRI scan, the anesthesia infusion, and a second fMRI scan. There is an optional follow-up fMRI scan one week post infusion.


Condition or disease Intervention/treatment Phase
Changes in Brain Network Connectivity Drug: Anesthetics, Dissociative Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Anesthesia and Brain Functional Connectivity: An Analysis of fMRI Changes in Chronic Pain and Refractory Depression
Study Start Date : February 2008
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Initial MRI
The subject will receive intravenous ketamine anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Drug: Anesthetics, Dissociative
The subject will receive intravenous anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Other Name: Ketamine

Experimental: Initial hospital
The subject will receive intravenous ketamine anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Drug: Anesthetics, Dissociative
The subject will receive intravenous anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Other Name: Ketamine

Experimental: Depression MRI
The subject will receive intravenous ketamine anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Drug: Anesthetics, Dissociative
The subject will receive intravenous anesthesia at a dose of 0.5mg/kg delivered over 40 minutes in a constant infusion or bolus plus infusion method to maintain steady state (10 minutes initial induction, 30 minutes steady-state, for 40 minutes total)
Other Name: Ketamine




Primary Outcome Measures :
  1. Functional Connectivity [ Time Frame: 8 minutes scans, acquired between 1 day and 3 days (see above) ]

    The imaging experiments and analysis of subject-specific data will lead to maps corresponding to separate measures: resting state functional connectivity maps. The outcome of interest is whether ketamine reduces functional connectivity between the anterior (subgenual anterior cingulate corte, sgACC) and posterior regions (posterior cingulate cortex, PCC) of the default mode network. This is the z-score of the functional connectivity correlation.

    Timepoints for Initial fMRI were: Time 1:Immediately before Infusion, Time 2: After washout (Approx. 40 min after end of infusion).

    Timepoints for Depression were: Time 1: 1 Day before Infusion, Time 2: 1 Day after Infusion




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Control Group:

Inclusion Criteria:

(4) Ability to tolerate small, enclosed spaces without anxiety; (6) English fluency.

Exclusion Criteria:

  • Pregnant or trying to become pregnant.
  • history of serious head injury;
  • possibility of ferrous metals within the body, e. g. aneurysm clips, retained particles; or metal that would impair the magnetic resonance (MR) signal, e.g., some dental hardware;
  • Smoking usage > 10 cigarettes per day
  • Daily intake of caffeine exceeds 2 cups of coffee per day
  • Unstable cardiac problems (e.g. severe or poorly treated hypertension, unstable arrhythmia, etc.) or concurrent medications for which anesthesia would be contraindicated
  • Patients with a current general medical illness that is life threatening or inadequately treated will be excluded: moderate-to-severe chronic pain, evidence of fracture or malignancy, inflammatory joint disease, severe physical impairment (e.g., bilateral amputation, blindness), morbid obesity, autoimmune/inflammatory diseases, cardiopulmonary disorders (i.e., angina, congestive heart failure, COPD), chronic renal insufficiency, uncontrolled endocrine or allergic disorders (i.e., hyper-/hypothyroidism, diabetes, allergic rhinitis), malignancy.
  • Taking any medication, prescription or non-prescription, with psychotropic effects.
  • History of psychiatric or neurological illness; History of substance abuse or dependence Positive urine toxicology screen.

Refractory Depression Group:

  • Meets all above control group screening criteria except history of psychiatric illness and prescription medication usage
  • Included subjects will have a Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) diagnosis of major depressive disorder, recurrent or chronic, moderate-to-severe, without psychotic features, with medication resistance, accepted with agreement by two different psychiatrists. For this study, treatment resistance is defined as ≥2 failed adequate antidepressant trials.
  • Patients with a DSM-IV diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder will be excluded. Any history of antidepressant- or substance- induced hypomania or mania will be excluded.
  • Subjects will be free of comorbid substance abuse or dependence for at least 3 months, with a negative urine toxicology screen.
  • No current suicide plan or intent.
  • Comorbid Axis I anxiety disorder diagnoses will be permitted if they do not require current treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02196259


Locations
United States, Michigan
University of Michigan - fMRI Laboratory
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Scott Peltier, PhD University of Michigan

Publications:

Responsible Party: Scott Peltier, Associate Research Scientist, Biomedical Engineering, University of Michigan
ClinicalTrials.gov Identifier: NCT02196259     History of Changes
Other Study ID Numbers: U028860-MICHR-Pilot
First Posted: July 22, 2014    Key Record Dates
Results First Posted: May 2, 2017
Last Update Posted: May 2, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Scott Peltier, University of Michigan:
Pre-Post

Additional relevant MeSH terms:
Anesthetics
Ketamine
Anesthetics, Dissociative
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action