Ketamine's Actions on Rumination Mechanisms as an Antidepressant

NCT04656886 | Completed

• 1 other identifier: HR14/15-0650
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

Rumination and anhedonia are two of the most common characteristics of depression that persist during remission and are not easily targeted by commonly prescribed antidepressants. Ketamine, an NMDA receptor antagonist, has emerged within the last decade as a potent, fast-acting antidepressant that can significantly improve anhedonia as early as two hours after a single infusion. The brain mechanisms, however, by which ketamine exerts its antidepressant action remain largely unknown. The aim of this study is to examine the early antidepressant action of ketamine, 2h post infusion, in patients who remitted from depression using fMRI. Participants are scanned while performing a personalised, autobiographical, emotional memory task and a monetary reward task. Ketamine is expected to reduce the activation of limbic areas such as the amygdala during emotional memory recall. Increased activations after ketamine are expected in reward processing areas, including striatal regions.

Conditions

Remission in Depression

Outcome Measures

Primary Outcomes (2)

• Ketamine's effects, 2h post infusion, on the activation of brain areas important for autobiographical emotional memory recall.

  To investigate the role of limbic areas and NMDA receptor blockade during autobiographical memory retrieval using fMRI

  1 YEAR

• Ketamine's effects, 2h post infusion, on the activation of brain areas important for reward processing and anhedonia.

  To investigate the role of striatal areas and NMDA receptor blockade during a monetary reward task using fMRI.

  1 YEAR

Study Arms (2)

Ketalar

EXPERIMENTAL

0.5mg/kg of ketalar (ketamine). Single, intravenous, steady state infusion over 40min.

Drug: Intravenous Infusion

Saline

PLACEBO COMPARATOR

Single, intravenous, steady state infusion over 40min.

Drug: Intravenous Infusion

Interventions

Intravenous Infusion DRUG

Ketalar; Saline

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Right-handed male and female volunteers with a history of depression between the ages of 18 and 50 years.
• Good command of the English language.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of and agrees to comply with all aspects of the study.
• Willing and able to comply with scheduled visits, dosing plan, laboratory trials and any other necessary procedures.
• Are willing for data to be shared and disseminated after being anonymised.

You may not qualify if:

• Have a current or previously diagnosed psychiatric disorder except depression.
• 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, hepatic or renal failure etc.).
• Show MR contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) which would render them unsuitable for the study.
• Have previously experienced an adverse response to ketamine.
• Have excessive use of alcohol (in excess of 28 units a week), caffeine (\>6 cups of coffee a day), or other drugs.
• 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 MRI scan).
• Have taken illicit drugs 7 days prior to admission, have consumed alcohol or caffeine within 24 hours prior to admission or have consumed nicotine within 4 hours prior to admission.
• Have taken grapefruit juice- or Seville orange-containing products 24 hours prior to admission.
• Use of any prescribed medication in the 3 weeks prior to enrolment or non-prescription medication (other than paracetamol) or herbal preparations in the previous 7 days.
• Have a significant history of drugs of abuse (including benzodiazepines) or positive drugs of abuse test.
• Had acute illness within 2 weeks before the start of study.
• Have clinically significant abnormalities in clinical chemistry (including liver function tests), haematology or urinalysis results.
• Have a history or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Have been diagnosed hypertension, or supine systolic BP outside of the range of 90 to 140 mmHg and a supine diastolic BP outside the range of 40 to 90 mmHg, after a period of acclimatisation

Sponsors & Collaborators

• King's College London: lead
• Johnson & Johnson: collaborator

Related Publications (4)

• Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

  PMID: 16894061 BACKGROUND

• Nolen-Hoeksema S. The role of rumination in depressive disorders and mixed anxiety/depressive symptoms. J Abnorm Psychol. 2000 Aug;109(3):504-11.

  PMID: 11016119 BACKGROUND

• Disner SG, Beevers CG, Haigh EA, Beck AT. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci. 2011 Jul 6;12(8):467-77. doi: 10.1038/nrn3027.

  PMID: 21731066 BACKGROUND

• Lally N, Nugent AC, Luckenbaugh DA, Ameli R, Roiser JP, Zarate CA. Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl Psychiatry. 2014 Oct 14;4(10):e469. doi: 10.1038/tp.2014.105.

  PMID: 25313512 BACKGROUND

MeSH Terms

Interventions

Infusions, Intravenous

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both the participants and the investigator are blind.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A group of remitted depressed participants will receive an intravenous infusion of ketamine or an inactive placebo, in a double-blind, cross over design. A minimun of 1 week is required between the two study sessions.

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 7, 2020
• Study Start: September 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: December 7, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share