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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05870501
Other study ID # 297200
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date October 20, 2021
Est. completion date September 11, 2023

Study information

Verified date March 2023
Source King's College London
Contact Peter Hawkins, PhD
Phone 02032283058
Email Ketamine-Signature@kcl.ac.uk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The main aim of this research is to explore the effects that ketamine has on the functional connectivity of the brain in participants with treatment resistant depression (TRD). This study will investigate the relationship between these changes and response to treatment as measured by clinical scales, as well as examining drug induced changes in reward and emotion based brain activity, structural connectivity, cerebral blood flow, cognition, metabolism and blood markers of brain plasticity.


Description:

A double-blind active-placebo crossover design will be used to study a single group of people with TRD to assess the effects of ketamine on brain networks activity versus an active placebo (midazolam). Participants will receive three separate IV infusions of ketamine (0.5mg/kg) followed by three separate IV infusions of an active placebo (midazolam (0.045mg/kg)), or 3 IV infusions of midazolam followed by 3 IV infusions of ketamine. Treatment order will be randomized in a crossover design. The study will consist of 11 visits including a screening visit, baseline assessments, and two main infusion periods each involving 3 separate IV infusions and a post infusion assessment visit 24 hrs after the third infusion. Ketamine or midazolam will be administered at each of the infusion periods in a crossover design. Assessment visits will include MRI, EEG and cognitive and clinical assessments. Up to 50 subjects will be enrolled to ensure that evaluable data is obtained from 45 subjects. The primary comparison will be within-subject between active treatment and placebo.


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Study Design


Intervention

Drug:
Ketamine
0.5mg/kg IV infusion
Midazolam
0.045mg/kg IV infusion

Locations

Country Name City State
United Kingdom The Institute of Psychiatry, Psychology & Neuroscience, King's College London London

Sponsors (2)

Lead Sponsor Collaborator
King's College London South London and Maudsley NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other To investigate the effects of ketamine on the cerebral metabolic rate of oxygen utilization (CMRO2) as a measure of brain tissue metabolism using fMRI The cerebral metabolic rate of oxygen can be assessed using specialised fMRI pulse sequences 24 hours post third IV infusion
Other Baseline measures of common genetic markers (SNPs) for genetic disease risk load Blood samples taken at baseline will be used for DNA analysis Baseline measure
Primary To investigate the effects of ketamine on brain resting state functional magnetic resonance imaging (fMRI) connectivity in patients with depression compared to placebo Change in resting state connectivity measured with fMRI Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on fMRI task-based activity during an emotional processing task compared to placebo Changes in task related fMRI activity using an emotional processing task (Region of Interest (ROIs): Anterior cingulate cortex (ACC), medial frontal cortex; whole brain analysis) Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on fMRI task-based activity during a reward-processing task compared to placebo Changes in task related fMRI activity using a reward processing task. (Regions of interest (ROIs): striatal, thalamic and prefrontal regions; whole brain analysis) Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on prolactin levels Blood samples analysed for prolactin levels at baseline, pre third infusion and post third infusion of ketamine and placebo Baseline and 40 minutes post third IV infusion
Secondary To investigate the effects of ketamine on anhedonic symptoms (as measured by SHAPS) compared to placebo The Snaith-Hamilton Pleasure Scale (SHAPS) is a self report scale of hedonic experience and is assessed at baseline and 24 hrs post infusion of ketamine and placebo. The scale ranges from 14-56, with a higher score indicating higher levels of anhedonia Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on depression symptoms (as measured by MADRS) compared to placebo The Montgomery-Asberg Depression Rating Scale is a interview based scale of depression symptoms and is assessed at baseline of each session and 24 hrs post infusion of ketamine and placebo. The scale ranges from 0-60, with a higher score indicating an higher severity of depression symptoms. Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on depression symptoms (as measured by QIDS) compared to placebo The Quick Inventory of Depressive Symptomatology-Self Report (QIDS) is a self report scale of depression symptoms and is assessed at baseline, pre infusion and 24 hrs post third infusion of ketamine and placebo The scale ranges from 0-42, with a higher score indicating an higher severity of depression symptoms. Baseline, pre infusion and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on the M3VAS compared to placebo The Maudsley 3-item Visual Analogue Scale (M3VAS) is a self report visual analogue scale (VAS) of three main domains of depression symptoms (mood, pleasure and suicidality) and is assessed at baseline, pre infusion and 24 hrs post third infusion of ketamine and placebo. The VAS ranges from 0-100 on each domain, with a higher score indicating an higher severity of that domain. Baseline, pre infusion and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on brain perfusion (ASL) compared to placebo Arterial spin labelling (ASL) is a measure of blood flow or perfusion in the brain. Measures are taken at baseline and 24 hours post third infusion of ketamine and placebo Baseline and 24 hours post third IV infusion
Secondary To investigate the blood plasma concentration (µg/mL) of ketamine following the third IV infusion Blood samples will be taken to measure the blood concentration of ketamine at specific time points post infusion 40 minutes, 120 minutes, 200 minutes and 24 hours post third IV infusion
Secondary To investigate the blood plasma concentration (µg/mL) of hydroxynorketamine following the third IV infusion Blood samples will be taken to measure the blood concentration of hydroxynorketamine (a metabolite of ketamine) at specific time points post infusion 40 minutes, 120 minutes, 200 minutes and 24 hours post third IV infusion
Secondary To investigate the blood plasma concentration (µg/mL) of norketamine following the third IV infusion Blood samples will be taken to measure the blood concentration of norketamine (a metabolite of ketamine) at specific time points post infusion 40 minutes, 120 minutes, 200 minutes and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on a short battery of cognitive tasks compared to placebo The Cognition is a self administered web-based battery of cognitive tasks that will be conducted at baseline, and 24 hours post third infusion of ketamine and placebo Baseline 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on blood biomarkers related to synaptogenesis compared to placebo Blood samples taken at baseline and 24 hours post third infusion of ketamine and placebo will be analysed for markers of synaptic plasticity (Brain derived neurotrophic factor (BDNF)) Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on the power of frequency bands (alpha, theta, gamma) in resting EEG Electroencephalogram (EEG) is an brain imaging technique that allows the recording of brain electrical activity and will be conducted at baseline, and 24 hours post third infusion of ketamine and placebo Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on structural connectivity (DTI) compared to placebo Diffusion tensor imaging (DTI) is a measure of brain tissue microstructure. Measures are taken at baseline and 24 hours post third infusion of ketamine and placebo Baseline and 24 hours post third IV infusion
Secondary To investigate the effects of ketamine on visual and auditory based ERPs compared to placebo Event related potentials (ERPs) are an EEG measure related to brain electrical activity that can be produced by visual and auditory stimuli Baseline and 24 hours post third IV infusion
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