Investigation of Intranasal Ketamine Related Changes in Attentional Brain Networks With Functional and Structural MRI

Investigation of Intranasal Ketamine Related Changes in Attentional Brain Networks With Functional and Structural MRI: a Placebo Controlled, Randomized, Cross-over Trial

Subanesthetic ketamine is currently used as a rapid-acting antidepressant. It is an antagonist of the N-methyl-d-aspartate (NMDA) receptor, but former results indicate that its action also depends on the noradrenaline system and the locus coeruleus (LC).

Based on this known impact of ketamine on the sympathetic nervous system the aim of this study is to investigate the effects of intranasal esketamine on LC related attentional brain networks in task based functional MRI, to relate those attention network changes to behavioural measures and to predict ketamine related attention network changes by brain structure.

Study Overview

• Status: Recruiting
• Conditions: Ketamine Treatment
• Intervention / Treatment: Drug: 56mg esketamine (2x Spravato® 28 mg nasal spray); Drug: 0.9% saline solution nasal spray

• Study Type: Interventional
• Enrollment (Anticipated): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Psychiatry and Psychotherapy
    • Contact: Rupert Lanzenberger, Assoc. Prof. PD MD; Phone Number: +43-1-40400-35760; Email: rupert.lanzenberger@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• General health (no serious internal or neurologic pre-existing conditions) based on medical history, physical examination and structured clinical interview for DSM-IV (SCID)
• Age 18 to 55 years
• Right-handedness (due to potential lateralization effects of left-handed subjects)
• Willingness and competence to sign the informed consent form

Exclusion Criteria:

• Current or history of psychiatric or neurological disease
• Current medical illness requiring treatment
• Current or former substance abuse
• Pregnancy or current breastfeeding
• Diagnosis of an Axis-1 psychotic disorder in a first-degree relative
• Known aneurysmal vascular disease based on medical history (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels), history of intracerebral haemorrhage, recent (within 6weeks) cardiovascular event, including myocardial infarction (MI)
• Significant pulmonary insufficiency, including COPD; sleep apnoea with morbid obesity (BMI ≥35), uncontrolled brady- or tachyarrhythmias that lead to haemodynamic instability; history of an MI, haemodynamically significant valvular heart disease or heart failure (NYHA Class III-IV)
• Hyperthyroidism that has not been sufficiently treated
• History of brain injury, hypertensive encephalopathy, intrathecal therapy with ventricular shunts, or any other condition associated with increased intracranial pressure
• Child-Pugh class C (severe) hepatic impairment
• Any contraindication for MRI (e.g., MR incompatible implants, etc.) including dental implants causing signal artifacts
• Failure to comply with the study protocol or to follow the instruction of the investigating team

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: first 56mg esketamine (2x Spravato® 28 mg nasal spray), then placebo	Drug: 56mg esketamine (2x Spravato® 28 mg nasal spray); 56mg esketamine (2x Spravato® 28 mg nasal spray); Drug: 0.9% saline solution nasal spray; 0.9% saline solution nasal spray
Experimental: first placebo (0.9% saline solution nasal spray), then ketamine	Drug: 56mg esketamine (2x Spravato® 28 mg nasal spray); 56mg esketamine (2x Spravato® 28 mg nasal spray); Drug: 0.9% saline solution nasal spray; 0.9% saline solution nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOLD response assessed with fMRI to arousal task	Blood oxygen level (BOLD) response assessed with functional magnetic resonance imaging (fMRI) during an arousal task	up to two weeks

Collaborators and Investigators

• Sponsor: Rupert Lanzenberger

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): April 22, 2024
• Study Completion (Anticipated): April 22, 2024

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 18, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: PSY-NIL-0011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No