A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders (GDKet)

• ClinicalTrials.gov Identifier: NCT04226963
• Recruitment Status: Recruiting
• First Posted: January 13, 2020
• Last Update Posted: January 13, 2020
• Sponsor: Medical University of Gdansk
• Information provided by (Responsible Party): Maria Galuszko-Wegielnik, Medical University of Gdansk

Tracking Information

• First Submitted Date: January 2, 2020
• First Posted Date: January 13, 2020
• Last Update Posted Date: January 13, 2020
• Actual Study Start Date: December 4, 2019
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2020)

• Incidence of adverse events assessed by Clinical-Administered Dissociative Symptoms Scale (CADSS) [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events will be assessed by Clinician-Administered Dissociative Symptoms Scale (change from baseline to each measure). Higher values represent a worse severity, but not necessarily outcome. The Clinical-Administered Dissociative Symptoms Scale has 23-items based on dissociative symptoms during the assessment. Each item is scored 0 (normal) to 4 (severe symptoms) with overall score ranges from 0 (normal) to 92 (severe symptoms). Total number of assessments:18 times
• Incidence of adverse events assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (BPRS) [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events will be assessed by 4-items positive symptoms subscale of Brief Psychiatric Rating Scale (change from baseline to each measure). Higher values represent a worse severity but not necessarily outcome. The 4-item positive symptoms subscale of Brief Psychiatric Rating Scale has 4-items based on conceptual disorganization, suspiciousness, hallucination and unusual thought content. Each item is scored 0 (normal) to 6 (severe symptoms) with overall score ranges from 0 (normal) to 24 (severe symptoms). Total number of assessments:18 times
• Incidence of adverse events assessed by body temperature (oral measurements) [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events assessed by body temperature (oral measurement) in Celsius degree - change from baseline to each measure. A normal range is from 36.2 to 38.0 Celsius degrees; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
• Incidence of adverse events assessed by blood pressure [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events assessed by blood pressure (after the participant has rested for at least 5 minutes) in mmHg - change from baseline to each measure. A normal range for systolic blood pressure is from 90 to 140 mmHg, for diastolic blood pressure is from 50 to 90 mmHg; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
• Incidence of adverse events assessed by respiration rate [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events assessed by respiration rate in a breath number per minute - change from baseline to each measure. A normal range for respiration is from 12 to 16 breaths per minute; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
• Incidence of adverse events assessed by pulse [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events assessed by pulse (beats per minute [bpm]) - change from baseline to each measure. A normal range for pulse is from 60 to 90 bpm; measurements beyond those ranges are clinically significant. The total number of measurements: 44 times
• Incidence of adverse events assessed by blood oxygen saturation [ Time Frame: Baseline through week 5 ]
  Incidence of adverse events assessed by blood oxygen saturation in percentage - change from baseline to each measure. A normal range for blood oxygen saturation is from 95 to 100 percentage; measurements under 95% are clinically significant. The total number of measurements: 44 times
• Incidence of adverse events assessed by weight [ Time Frame: Baseline and week 5 ]
  Incidence of adverse events assessed by weight in kilograms- change from baseline to each measure. Gain weight for 7% baseline weight is clinically significant. Total numbers of assessments: 2. Weight and height will be combined to report BMI in kg/m^2
• Incidence of adverse events assessed by height [ Time Frame: Baseline ]
  Incidence of adverse events assessed by height in meters. Total numbers of assessments: 1. Weight in kilograms and height in meters will be combined to report BMI in kg/m^2

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 10, 2020)

Change in severity of depression symptoms assessed by Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline through week 5 ]

Change in severity of depression symptoms from baseline to each measure. Higher values represent a worse severity, but not necessarily outcome. The MADRS has 10-items which are based on mood symptoms over the past 7 days. Each item is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders
• Official Title: A Naturalistic Study of Ketamine for Treatment Resistant Mood Disorders: Gdansk Depression Ketamine Project
• Brief Summary: This study aims to openly test the long-term safety, tolerability and effectiveness of repeated administration of IV, nasal spray and oral ketamine for treatment-resistant mood disorders.
• Detailed Description: Current pharmacological treatments for depression prove unsatisfactory efficacy with a proportion of subjects demonstrating treatment-resistant depression (TRD). The observation applies both to major depressive disorder (MDD) as well as bipolar I depression. There is growing evidence that the glutamatergic system plays a role in the pathophysiology and treatment of depression. Discovery of rapid, although transient antidepressant effect of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in a single sub-anaesthetic intravenous dose in unipolar, bipolar and treatment-resistant patients provides evidence for a glutamatergic antidepressant. Subsequent studies confirmed this effect in repeated doses. Further research demonstrated that repeated ketamine infusions result in sustainable antidepressant effect with both, twice-weekly and thrice-weekly administration schedules. However, the worsening of depression may occur after infusions are completed. Given the risk of relapses, there is a definite need for the development of new strategies to maintain the beneficial effects of ketamine treatment. In the present study, the investigators aim to openly assess the safety, tolerability, and effectiveness of repeated, individually tailored IV, nasal spray and oral ketamine for treatment-resistant mood disorders. The investigators intend to explore questions regarding optimal dose, treatment frequency and duration.
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 1 Week
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Inpatients with TRD referred to the tertiary-reference unit for mood disorders

Condition

• Treatment Resistant Depression
• Bipolar Depression
• Ketamine
• Major Depressive Disorder

Intervention

Drug: Ketamine

Ketamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks) Ketamine will be given in intranasal spray twice weekly over a period of 4 weeks Ketamine will be given orally (solution 2.0mg/kg, 2.5mg/kg) twice weekly over a period of 4 weeks.

• Study Groups/Cohorts: Not Provided

Publications *

• Włodarczyk A, Cubała WJ, Gałuszko-Węgielnik M, Szarmach J. Dissociative symptoms with intravenous ketamine in treatment-resistant depression exploratory observational study. Medicine (Baltimore). 2021 Jul 23;100(29):e26769. doi: 10.1097/MD.0000000000026769.
• Włodarczyk A, Cubała WJ, Gałuszko-Węgielnik M, Szarmach J. Central nervous system-related safety and tolerability of add-on ketamine to antidepressant medication in treatment-resistant depression: focus on the unique safety profile of bipolar depression. Ther Adv Psychopharmacol. 2021 May 19;11:20451253211011021. doi: 10.1177/20451253211011021. eCollection 2021.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 10, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Major depressive disorder (MDD) or bipolar disorder (BD) diagnosis as provided by DSM-5 criteria
2. TRD defined as the patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose of at least two trials of first-line evidence-based treatments and/or electroconvulsive therapy (ECT)

Exclusion Criteria:

1. Pregnancy and lactation
2. Hypersensitivity to ketamine
3. Uncontrolled hypertension
4. Other uncontrolled somatic diseases that may impact safety per investigators judgement

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Maria Gałuszko-Węgielnik, MD PhD; +48 58 3492650; mgaluszko@gumed.edu.pl

Contact: Wiesław J. Cubała, MD PhD; +48 58 3492650; cubala@gumed.edu.pl

• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT04226963
• Other Study ID Numbers: NKBBN/172-674/2019
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Maria Galuszko-Wegielnik, Medical University of Gdansk
• Study Sponsor: Medical University of Gdansk
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Medical University of Gdansk
• Verification Date: January 2020