Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine
- Conditions
- Depressive Disorder, Treatment-Resistant
- Interventions
- Registration Number
- NCT04977674
- Lead Sponsor
- King's College London
- Brief Summary
The overarching aim of this research is to determine the acute effects of ketamine on brain glutamate, functional connectivity and cerebral blood flow in treatment-resistant depression, explore whether the effects are attenuated by the opioid receptor antagonist naltrexone and relate these findings to antidepressant response.
- Detailed Description
The study is a randomised, double-blind, crossover design with two treatment conditions: oral placebo or oral naltrexone preceding ketamine infusion during neuroimaging in subjects with treatment-resistant depression.
Each subject will participate in two imaging sessions on two separate days. Each subject will receive a dose of ketamine (IV infusion, 0.5 mg/kg over 40 minutes) during each scan. Subjects will receive either oral placebo or naltrexone 50 mg, 45 minutes before the initiation of each of the ketamine infusions.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine Naltrexone Participants randomly assigned to arm A: VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. VISIT 2) Placebo before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days. A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine Placebo Participants randomly assigned to arm A: VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. VISIT 2) Placebo before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days. A: Visit 1) Naltrexone + Ketamine, Visit 2) Placebo + Ketamine Ketamine Participants randomly assigned to arm A: VISIT 1) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. VISIT 2) Placebo before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days. B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine Placebo Participants randomly assigned to arm B: VISIT 1) Placebo before the administration of ketamine 0.5mg/kg. VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days. B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine Naltrexone Participants randomly assigned to arm B: VISIT 1) Placebo before the administration of ketamine 0.5mg/kg. VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days. B: Visit 1) Placebo + Ketamine, Visit 2) Naltrexone + Ketamine Ketamine Participants randomly assigned to arm B: VISIT 1) Placebo before the administration of ketamine 0.5mg/kg. VISIT 2) Naltrexone 50mg before the administration of ketamine 0.5mg/kg. Study visits are separated by 14-28 days.
- Primary Outcome Measures
Name Time Method Change in Glutamate Changes will be in the same session comparing the ketamine infusion period to the pre-ketamine infusion baseline Compare changes in glutamate and GLX (glutamate +glutamine), referenced to total creatine (tCr), during ketamine infusion as measured by functional magnetic resonance spectroscopy (1H-fMRS) for naltrexone versus placebo pre-treatment conditions.
Hypothesis: There will be a significant increase in glutamate measures during ketamine administration compared to a resting baseline condition in a medial prefrontal cortex (mPFC) /anterior cingulate cortex (ACC) region. Pre-treatment with naltrexone will attenuate this increase.
- Secondary Outcome Measures
Name Time Method Change in Resting State Functional Connectivity Changes will be in the same session comparing post-infusion (immediately after ketamine infusion) to the pre-ketamine infusion baseline Compare changes in functional connectivity as measured by resting state-fMRI post-ketamine administration for naltrexone versus placebo pre-treatment conditions.
Hypotheses:
1. Ketamine administration will lead to significant reductions in functional brain connectivity between the subgenual anterior cingulate cortex (sgACC), default mode network (DMN) regions of interest (mPFC and posterior cingulate cortex (PCC)), thalamus, insula and ventral tegmental area (VTA) compared to a resting baseline condition. Pre-treatment with naltrexone will attenuate these reductions.
2. Ketamine administration will lead to a significant increase in functional brain connectivity between the sgACC and dorsolateral prefrontal cortex (DLPFC) compared to a resting baseline condition. Pre-treatment with naltrexone will attenuate this increase.Change in Cerebral Blood Flow Changes will be in the same session comparing data collected 30 minutes after the ketamine infusion commences to the pre-ketamine infusion baseline Compare changes in cerebral blood flow during ketamine infusion as measured by arterial spin labelling (ASL) for naltrexone versus placebo pre-treatment conditions.
Hypothesis: Ketamine administration will lead to a significant increase in CBF in sgACC, pregenual ACC (pgACC), dorsal ACC (dACC) and thalamus regions of interest compared to a resting baseline condition. Pre-treatment with naltrexone will attenuate these increases.
Trial Locations
- Locations (1)
King's College London
🇬🇧London, United Kingdom