Neuroplasticity Induced by General Anaesthesia (DANA1)

August 19, 2021 updated by: Signe Sloth Madsen
The aim of this study is to use magnetic resonance imaging to explore and compare possible de novo neuroplastic changes induced by the isolated effects of the hypnotic agents sevoflurane and propofol, respectively. In addition, to explore possible associations between neuroplastic changes and clinical and/or biochemical outcomes. It is a randomised, cross-over, single blinded clinical study. N = 30. Female:male ratio 1:1.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

In the perioperative period, severe changes can be observed in the endocrine, immune, and nervous system. These changes are called the surgical stress response. Clinically, this can be observed as increased pain response and disturbances in the circadian rhythm, memory, cognitive and executive functions, and may lead to post-operative delirium. The post-operative cognitive dysfunction is associated with increased mortality and risk of prematurely leaving occupation. Post-operative delirium with fluctuating levels of attention and consciousness is a serious condition associated with poor outcome, including longer hospitalisation and increased early mortality.

General anaesthesia may contribute to the surgical stress response. Some data indicate that general anaesthesia per se can cause alterations and disturbances in the brain such as sleep and circadian disturbances. Recent evidence suggests that anaesthetic agents may impair neurogenesis and cause memory impairment. In addition, inhalation anaesthesia may result in more cerebral disturbances compared to total intravenous anaesthesia (TIVA). In this study, we will isolate the effects of the two primary hypnotic agents used in general anaesthesia, sevoflurane and propofol, without the interactions and confounders of polypharmacy and varying levels of disease among a surgical population.

Materials

The study consists of two study sessions. In each study session magnetic resonance imaging (MRI) scans will be obtained before and after general anaesthesia, and in addition after one and eight days.

The following imaging modalities will be employed: (i) T1-weighted 3D anatomy (T1w3D), (ii) Diffusion Tensor Imaging (DTI), (iii) resting state functional MRI (rsfMRI). The MRI scans will be supplemented with cognitive testing, sleep evaluation and blood sampling. Thus, the set-up for each volunteer will be:

Session one:

Day 0: MRI 1, cognitive testing, questionnaires, and blood sampling. General anaesthesia (maintenance phase with sevoflurane OR propofol according to randomisation), and post-anaesthesia care. MRI 2 and repeated cognitive testing, questionnaires, and blood sampling.

Day +1: MRI 3, cognitive testing, questionnaires, and blood sampling.

Day +8: MRI 4, cognitive testing, and questionnaires.

Session two: Identical to session one, except the volunteer will receive the remaining type of general anaesthesia (sevoflurane or propofol, opposite to session one).

Data evaluation will be conducted with assessor blinded to anaesthesia type.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Capital Region
      • Glostrup, Capital Region, Denmark, 2600
        • Department of Neuroanaesthesiology
      • Glostrup, Capital Region, Denmark, 2600
        • Functional Imaging Unit, Department for Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Glostrup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 and ≤35.
  • Healthy individual.
  • BMI ≥18 kg/m2 and ≤30kg/m2.
  • Normal electrocardiogram (ECG).
  • Normal physical examination, including neurological examination, auscultation of the heart and lungs, and measurement of blood pressure and pulse.
  • American Society of Anaesthesiologists (ASA) class 1.
  • Mallampati I-II and simplified airway risk index (SARI) 0-2 (i.e. no indication of difficult intubation). See appendix for details.
  • Right-handed.
  • Female participants must use safe contraceptives (hormonal or mechanical, including intrauterine devices).
  • Speaks and understand Danish.
  • Provides oral and written informed consent.

Exclusion Criteria:

  • Contraindications to MRI.
  • Left-handedness or ambidexterity.
  • History of complications to general anaesthesia, including malignant hyperthermia.
  • Family history of malignant hyperthermia.
  • Known incident of malignant hyperthermia or any unexplained complication to general anaesthesia among close relatives.
  • Allergy to any kind of medication or material to which the volunteer could be exposed during this study.
  • History of serious illness.
  • History of cancer, immune disease, autoimmune disease, chronic pain or neurological / psychiatric illness.
  • Major trauma or head trauma with any symptoms present at the time of inclusion.
  • Surgery less than six weeks prior to the study period.
  • Infection (with fever) less than two weeks prior to or during the study sessions.
  • Daily use of any medication (not counting contraceptives).
  • Consumed anti-depressants during the last 30 days before study days.
  • Weakly intake of >21 (for females >14) units of alcohol.
  • Heavy intake of caffeine (> 5 cups/day).
  • Smoking during the last 30 days before study days.
  • Substance abuse (assessed by the investigator).
  • Pregnancy
  • Reflux or dyspepsia.
  • Poor dental status or oral health.
  • Expected or suspected difficult airway.
  • Declines receiving information regarding accidental pathological findings during MRI scans of the brain.
  • Cannot cooperate to tests.
  • Otherwise judged unfit for participation by the investigator.

Exclusion Criteria during the study:

  • Any of the above-mentioned exclusion criteria.
  • Major trauma or head trauma during the study period.
  • Surgery during the study period.
  • Infection (with fever) during the study period.
  • Consumption of more than 3 units of alcohol within 24 hours before each study day (intervention day or MRI scan day)
  • Consumed analgesics within 3 days before each study day
  • Consumed anti-histamines less than 48 hours before each study day
  • Intake of caffeine 12 h prior to each study day
  • Smoking

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sevoflurane-Propofol

Session one: Sevoflurane as maintenance anaesthetic during general anaesthesia.

Session two: Propofol as maintenance anaesthetic during general anaesthesia.
Drug: Sevoflurane-propofol
General anaesthesia with a maintenance phase of two hours duration with either sevoflurane or propofol.
Other Names:
  • Propofol-sevoflurane
Active Comparator: Propofol-Sevoflurane

Session one: Propofol as maintenance anaesthetic during general anaesthesia.

Session two: Sevoflurane as maintenance anaesthetic during general anaesthesia.
Drug: Sevoflurane-propofol
General anaesthesia with a maintenance phase of two hours duration with either sevoflurane or propofol.
Other Names:
  • Propofol-sevoflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in T1w3D
Time Frame: 8 days
Volume and morphology of selected brain regions and anatomical structures as recorded by T1w3D anatomy MRI.
8 days
Changes in DTI
Time Frame: 8 days
White matter microstructure as measured using Diffusion Tensor Imaging (DTI)
8 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in rsfMRI
Time Frame: 8 days
Differences in resting state functional MRI induced by general anaesthesia
8 days
Changes in fatigue
Time Frame: 8 days
Differences in severity and characteristics of fatigue related to general anaesthesia, as measured by Multidimensional Fatigue Inventory (MFI-20, a scale of 0-5 in each of 20 questions, with higher scores indicating more fatigue).
8 days
Cognitive performance
Time Frame: 8 days
Changes in cognitive function related to general anaesthesia, measured with a combination of Test of Attentional Performance, Paced Auditory Serial Addition Test and Conners Continuous Performance Test.
8 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Signe Sloth Madsen

Investigators

  • Principal Investigator: Signe Madsen, MD, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2019

Primary Completion (Actual)

August 13, 2021

Study Completion (Actual)

August 13, 2021

Study Registration Dates

First Submitted

October 10, 2019

First Submitted That Met QC Criteria

October 11, 2019

First Posted (Actual)

October 14, 2019

Study Record Updates

Last Update Posted (Actual)

August 20, 2021

Last Update Submitted That Met QC Criteria

August 19, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-18028925

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The responsible investigators will consider data sharing, considered compliance with General Data Protection Regulation (GDPR) regulations and data sharing agreement.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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