Racemic Ketamine Versus S-ketamine With Arterial Spin Labeling (ASL)-MRI in Healthy Volunteers
Information source: Lund University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Abnormal Vascular Flow
Intervention: Racemic ketamine (Drug); S-ketamine (Drug)
Phase: N/A
Status: Completed
Sponsored by: Lund University Official(s) and/or principal investigator(s): Jonas Åkeson, profesor, Study Director, Affiliation: Lund University
Summary
Racemic ketamine and S-ketamine are used in clinical practice today. Little is known of
their difference in effect on cerebral blood flow, volume and metabolism. cerebral blood
flow (CBF) measuring techniques are limited in time so constant measurement to mirror a
dynamic process is impossible or very difficult. A novel MRI application, arterial spin
labeling, offers the possibility that without radiation or contrast, to measure
semi-continuous CBF with measurements every 60-120 seconds. The investigators will give 14
healthy volunteers both study drugs in a randomised sequence with one week apart and measure
regional CBF during the study period of 45 minutes after a sub-anaesthetic bolus dose of 0,6
mg/kg racemic ketamine and 0,3 mg/kg S-ketamine The investigators hypothesize that there is
no difference between racemic ketamine and S(+)-ketamine with regards to Arterial Spin
Labeling (ASL) measured cerebral blood flow.
Clinical Details
Official title: A Prospective Randomised, Double-blinded Cross-over Study to Investigate the Effects of Racemic and S-ketamine on Cerebral Blood Flow on Healthy Volunteers With MRI-ASL
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
Primary outcome: regional cerebral blood flow
Detailed description:
In this investigator-initiated randomised, double-blinded, crossover study, adult healthy
volunteers will be randomised to receive, as 60-second iv bolus injections on two different
occasions with at least seven days interval, 0. 3 mg kg of S-ketamine (Ketanest® 5. 0 mg/ ml,
Pfizer, USA) or 0. 6 mg/kg of racemic ketamine (Ketalar® 10 mg/ml, Pfizer, USA) supplied by
the hospital pharmacy.
The volunteers will consecutively be given specific inclusion numbers and randomized
according to a schedule with corresponding randomization codes prepared in advance by the
Research & Development Centre of the Skåne Region, Skåne University Hospital, Lund, Sweden.
Before each investigation, a sealed envelope marked with the corresponding inclusion number,
will be opened in a separate room by a nurse not taking further part in the study. The nurse
prepared the study drug according to the randomization code in a 20 ml syringe based on a
bodyweight-based dosing schedule, and diluted the study drug with saline to a total volume
of 20 ml. The prepared syringe, marked with the inclusion number, date and signature, will
be handed over to the investigator.
After an initial 10-minute period of dynamic baseline measurements, the study drug will be
injected manually by the investigator. ASL measurements will be made over a 45-minute study
period starting from the injection of study drug, and the volunteer will be brought to the
preparation room for at least 60 minutes of further supervision until clinical routine
criteria for postoperative discharge will be met.
Fourteen healthy (American Society of Anaesthesiologists physical status 1) adult volunteers
will be included after physical examinations and individual written informed consents.
Female subjects will be required to use effective anti-conception methods during the study
period. The volunteers will have to refrain from caffeine, nicotine, alcohol and medications
for 72 hours, and fast for six hours, but will be allowed to drink water until two hours
before each ASL-MRI investigation.
Each volunteer will be offered ear plugs, asked to rest with eyes closed during the scanning
procedure, and left undisturbed throughout the study period. Oxygen 2 l/min will be
delivered by nasal cannula.
A hand vein will be cannulated with a 20 G (1. 1 mm) 45 mm teflon catheter for injection of
study drug, and a balanced glucose solution will be infused at a rate of 1. 0 ml/kg/h iv. The
radial artery will be cannulated at wrist level with a 20 G 45 mm teflon catheter after
local infiltration with 2-3 ml of lidocaine. Each volunteer will be connected to an
N-MRI2-01 monitoring device recording the ECG, invasive blood pressure, SpO2, ETCO2 and
respiratory rate.
Monitored data will be sampled minutely throughout the study period, saved onto a PC card
and analyzed with the Datex-Ohmeda S/5Collect version 4. 0™ software package.
Arterial blood for blood gas analysis was obtained at baseline and at 1, 5, 10 and 15 min
after injection of the study drug. Analyses were made on a Radiometer ABL800 FLEX device The
ASL data will be acquired using a 3 Tesla MRI unit. A three-dimensional (3D) GRASE pulse
sequence will be employed (2), using a labeling and saturation schedule based on FAIR (3)
and Q2TIPS (4).
Drug-induced changes in regional perfusion will be monitored over time using a single
inversion time (TI) of 2000 ms and repeated 115 times, and a repetition time (TR) of 3000
ms. For multiple TI, ten time points were acquired with a starting point at TI = 300 ms and
an increment of 300 ms between time points, the total inflow time was 1400 ms and the TR was
set to 3700 ms.
Data sets will be preprocessed using realign tools of the Statistical Parameters Mapping
version 8. 0 (SPM8) software package (Wellcome Department of Imaging Neuroscience, London,
UK; http://www. fil. ion. ucl. ac. uk/spm) and executed in the Matlab 7. 11 software package. The
labeled and control images will be pair-wise subtracted to produce CBF-weighted ASL images
from re-aligned control/tag images, and these difference maps were denoised using an
established wavelet-domain filtering method (5), and an in-house software program written in
IDL 7. 1 (ITT Visual Information Solutions, Boulder, CO, USA). Values of CBF (in ml/100g/min)
will be calculated using a general kinetic model (6) according to the Buxton equation CBF
values will be determined by drawing different numbers of symmetrical cerebral regions of
interest (ROI) bilaterally to outline the grey matter of the frontal lobes, parietal lobes,
temporal lobes, occipital lobes, insular cortex, anterior cingulate, posterior cingulate,
thalamus, caudate nucleus and putamen. Global CBF values will determined by drawing a large
ROI to outline the whole brain tissue within the skull.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- healthy (ASA 1),
- age 18-65 years,
- fertile women must use approved anticonception during study period (2 weeks)
Exclusion Criteria:
- known or suspected pregnancy,
- BMI < 30,
- motion sickness,
- claustrophobia,
- somatic or psychiatric disease,
- drug abuse,
- chronic medication,
- drug allergy,
- difficulties in understanding the written and spoken Swedish language
Locations and Contacts
Deprtment of radiology, SUS, Malmö, Malmö 205 02, Sweden
Additional Information
Starting date: May 2011
Last updated: February 20, 2012
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