NCT05870501

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Oct 2021

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 20, 2021

Completed
1.4 years until next milestone

First Submitted

Initial submission to the registry

March 6, 2023

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 23, 2023

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 13, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 13, 2023

Completed
Last Updated

November 18, 2024

Status Verified

September 1, 2023

Enrollment Period

1.9 years

First QC Date

March 6, 2023

Last Update Submit

November 15, 2024

Conditions

Depressive DisorderDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantBipolar DisorderBipolar Disorder IBipolar Disorder IIMood DisordersAnhedonia

Keywords

DepressionBipolar DisorderMajor Depressive DisorderMDDTreatment-Resistant DepressionKetamine

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (16)

  • To investigate the effects of ketamine on fMRI task-based activity during an emotional processing task compared to placebo

    Baseline and 24 hours post third IV infusion

  • To investigate the effects of ketamine on fMRI task-based activity during a reward-processing task compared to placebo

    Baseline and 24 hours post third IV infusion

  • To investigate the effects of ketamine on prolactin levels

    Baseline and 40 minutes post third IV infusion

  • To investigate the effects of ketamine on anhedonic symptoms (as measured by SHAPS) compared to placebo

    Baseline and 24 hours post third IV infusion

  • To investigate the effects of ketamine on depression symptoms (as measured by MADRS) compared to placebo

    Baseline and 24 hours post third IV infusion

  • +11 more secondary outcomes

Other Outcomes (2)

  • To investigate the effects of ketamine on the cerebral metabolic rate of oxygen utilization (CMRO2) as a measure of brain tissue metabolism using fMRI

    24 hours post third IV infusion

  • Baseline measures of common genetic markers (SNPs) for genetic disease risk load

    Baseline measure

Study Arms (2)

Ketamine followed by midazolam

EXPERIMENTAL

Ketamine 0.5mg/kg (three IV infusions) followed by midazolam 0.045mg/kg (three IV infusions)

Drug: KetamineDrug: Midazolam

Midazolam followed by ketamine

EXPERIMENTAL

Midazolam 0.045mg/kg (three IV infusions) follower by ketamine 0.5mg/kg (three IV infusions)

Drug: KetamineDrug: Midazolam

Interventions

KetamineDRUG

0.5mg/kg IV infusion

Ketamine followed by midazolamMidazolam followed by ketamine
MidazolamDRUG

0.045mg/kg IV infusion

Ketamine followed by midazolamMidazolam followed by ketamine

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Be male or female, aged between 18 and 55 years of age inclusive.
  • Have a diagnosis of MDD, Bipolar 1 or Bipolar 2 depression and fulfil criteria for TRD depression. TRD patients are defined as having inadequately responded to at least two courses of antidepressants, given in a therapeutic dose and duration (Fekadu et al., 2018).
  • Have moderate to severe depression symptoms as demonstrated by a MADRS score greater than 20.
  • Be physically healthy, defined as having no clinically relevant abnormalities identified by a detailed medical history and full examination including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests
  • Have a good command of the English language.
  • Have no or very little knowledge of the Chinese language.
  • Provide a personally signed and dated informed consent document indicating that the participant has been informed of and agrees to comply with all aspects of the study.
  • Be willing and able to comply with scheduled visits, dosing plan, laboratory trials and any other necessary procedures.

You may not qualify if:

  • Have a current diagnosed psychiatric disorder, except MDD, Bipolar 1 and Bipolar 2 disorders and comorbid generalised anxiety disorder (GAD), social anxiety and/or social phobia.
  • Have a current or previously diagnosed psychotic disorder: Schizophrenia, Schizoaffective Disorder, Delusional disorder, Schizophreniform disorder, Schizotypal (personality) disorder, or Brief psychotic disorder.
  • Have previously failed Ketamine as an antidepressant treatment given at a therapeutic dose.
  • Have previously experienced an adverse response to ketamine and/or midazolam.
  • Have scored 70 or lower in the WASI at the screening visit.
  • Have one or more immediate family members with a current or previously diagnosed psychotic disorder.
  • Have a medically significant condition which renders them unsuitable for the study (e.g., diabetes, severe cardiovascular disease, severe respiratory disease (e.g. COPD), hepatic or renal failure etc.).
  • Be pregnant or breastfeeding, if female.
  • Have any MR contra-indications (e.g., metal implants, pacemakers, claustrophobia etc.) which would render them unsuitable for the study.
  • Currently consume alcohol in excess of 28 units a week or more than 6 cups of caffeinated drinks per day.
  • Smoke more than 5 cigarette per day
  • Have taken illicit drugs 7 days prior to admission or current use of drugs of abuse including amphetamines, MDMA, cannabis and opioids Have taken any other medication during the course of the study that has not been discussed. This should be documented by the investigators. (As an exception, 1g paracetamol/24 hours may be taken up to 24 hours prior to any visit).
  • Have consumed alcohol or caffeine within 12h and/or nicotine 4h hours prior to the screening visit, study day 1, 2 and 3 and each infusion visit until discharged at the end of each of those visits.
  • Have consumed grapefruit juice or Seville oranges-containing products 24 hours prior to admission.
  • Have used any prescribed medication in the 3 weeks prior to enrolment or non-prescription medication (other than paracetamol) in the previous 7 days, excluding medication prescribed for bipolar I and II and MDD.
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Institute of Psychiatry, Psychology & Neuroscience, King's College London

London, SE5 8AF, United Kingdom

Location

MeSH Terms

Conditions

Depressive DisorderDepressive Disorder, MajorDepressive Disorder, Treatment-ResistantBipolar DisorderMood DisordersAnhedoniaDepression

Interventions

KetamineMidazolam

Condition Hierarchy (Ancestors)

Mental DisordersBipolar and Related DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Mitul Mehta, PhD

    King's College London

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: 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 be randomised to receive three separate IV infusions of ketamine (0.5mg/kg) followed by three separate IV infusions of midazolam (0.045mg/kg), or three separate infusions of midazolam followed by three separate infusions of ketamine.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 6, 2023

First Posted

May 23, 2023

Study Start

October 20, 2021

Primary Completion

September 13, 2023

Study Completion

September 13, 2023

Last Updated

November 18, 2024

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)