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Music as an Intervention to Improve Hemodynamic Tolerability of Ketamine in Depression

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ClinicalTrials.gov Identifier: NCT04701866
Recruitment Status : Recruiting
First Posted : January 8, 2021
Last Update Posted : January 8, 2021
Sponsor:
Collaborator:
Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés
Information provided by (Responsible Party):
Stéphane Richard-Devantoy, Douglas Mental Health University Institute

Tracking Information
First Submitted Date  ICMJE January 4, 2021
First Posted Date  ICMJE January 8, 2021
Last Update Posted Date January 8, 2021
Estimated Study Start Date  ICMJE January 11, 2021
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
Changes in Systolic Blood Pressure [ Time Frame: From 0 to 40 minutes of each infusion. ]
For the primary outcome data analysis, we will adopt the generalized linear model (GLM) to investigate the change in systolic blood pressure (SBP) at 40 minutes versus at 0 minutes between intervention and control groups. Specifically, we treat the difference between the average of the triplicate SBP measurements (measured by a calibrated Welch Allyn Blood Pressure Device at 0 minutes and the average of the triplicate SBP measurements at 40 minutes at each infusion as the outcomes in the GLM, adjusting for covariates such as intervention, age and sex. The generalized estimating equation (GEE) technique is proposed to estimate the regression coefficients, and the corresponding variances are estimated by the sandwich estimators.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2021)
  • Change From Baseline in MADRS Total Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 6 (item's symptoms are severe). The total possible score is 60. Higher scores indicate greater severity.
  • Change From Baseline in MADRS Total Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 6 (item's symptoms are severe). The total possible score is 60. Higher scores indicate greater severity.
  • Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Beck Depression Inventory Scale is a 21-item, patient-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 3 (item's symptoms are severe). The total possible score is 63. Higher scores indicate greater severity.
  • Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Beck Depression Inventory Scale is a 21-item, patient-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 3 (item's symptoms are severe). The total possible score is 63. Higher scores indicate greater severity.
  • Change From Baseline in Clinician-Rated Global Impression Improvement Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Clinician-Rated Global Impression Improvement score (CGI-I) rates improvement with treatment from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Severity Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Clinician-Rated Global Impression Severity score (CGI-S) rates severity of illness from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Clinician-Rated Global Impression Suicidality Severity score (CGI-SS) rates severity of suicidality from 1 to 5, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Clinician-Rated Global Impression Suicidality Improvement score (CGI-SI) rates the improvement in suicidality from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Improvement Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Clinician-Rated Global Impression Improvement score (CGI-I) rates improvement with treatment from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Severity Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Clinician-Rated Global Impression Severity score (CGI-S) rates severity of illness from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Clinician-Rated Global Impression Suicidality Severity score (CGI-SS) rates severity of suicidality from 1 to 5, with higher scores indicating a worse outcome.
  • Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Clinician-Rated Global Impression Suicidality Improvement score (CGI-SI) rates the improvement in suicidality from 1 to 7, with higher scores indicating a worse outcome.
  • Change From Baseline in PSQI Total and Subscores to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Pittsburgh Sleep Quality Index (PSQI) contains 19 self-rated questions. The answers refer to the majority of days and nights in the past month. The 19 items are combined to form 7 components, rated from 0 (no difficulty) to 3 (severe difficulty), for a sum of 21 points. A low score indicates better outcome.
  • Change From Baseline in PSQI Total and Subscores to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Pittsburgh Sleep Quality Index (PSQI) contains 19 self-rated questions. The answers refer to the majority of days and nights in the past month. The 19 items are combined to form 7 components, rated from 0 (no difficulty) to 3 (severe difficulty), for a sum of 21 points. A low score indicates better outcome.
  • Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Beck Scale for Suicide Ideation (Current) consists of 19 statements to be rated by the participant on a scale of 0 to 2. A lower score means better outcome.
  • Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Beck Scale for Suicide Ideation (Current) consists of 19 statements to be rated by the participant on a scale of 0 to 2. A lower score means better outcome.
  • Change From Baseline in Psychological and Physical Pain to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The Visual-Analogue Scales of Psychic and Physical pain consists of two sets of 3 10cm scales. Participants note with a vertical line the intensity of their pain; currently, maximally in the past 15 days, and average over the past 15 days. The left limit indicates "0" pain whereas the right bound indicates "maximal" pain.
  • Change From Baseline in Psychological and Physical Pain to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The Visual-Analogue Scales of Psychic and Physical pain consists of two sets of 3 10cm scales. Participants note with a vertical line the intensity of their pain; currently, maximally in the past 15 days, and average over the past 15 days. The left limit indicates "0" pain whereas the right bound indicates "maximal" pain.
  • Change From Baseline in STAI-Y A to Last Treatment [ Time Frame: Baseline, Day 23 ]
    The State-Trait Anxiety Scale (STAI-Y A) consists of 20 participant-rated statements, from 1 to 4 (1= Not at all, 4= Very much so) regarding their current anxiety (state). A lower score corresponds to less severity of symptoms.
  • Change From Baseline in STAI-Y A to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The State-Trait Anxiety Scale (STAI-Y A) consists of 20 participant-rated statements, from 1 to 4 (1= Not at all, 4= Very much so) regarding their current anxiety (state). A lower score corresponds to less severity of symptoms.
  • Change From Baseline in STAI-Y B to Last Treatment [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The State-Trait Anxiety Scale (STAI-Y B) consists of 20 participant-rated statements, from 1 to 4 (1= Not at all, 4= Very much so) regarding their longstanding anxiety (trait). A lower score corresponds to less severity of symptoms.
  • Change From Baseline in STAI-Y B to Follow-up [ Time Frame: Baseline, 1-month follow-up (8 weeks) ]
    The State-Trait Anxiety Scale (STAI-Y B) consists of 20 participant-rated statements, from 1 to 4 (1= Not at all, 4= Very much so) regarding their longstanding anxiety (trait). A lower score corresponds to less severity of symptoms.
  • The Mystical Experience Questionnaire (MEQ) after each treatment [ Time Frame: Immediately after the interventions ]
    The Mystical Experience Questionnaire consists of 30 statements to rate from 0 (none) to 5 (extreme). Possible scores range from 0 to 150 with higher scores indicating greater mystical experiences.
  • The Psychedelic Music Questionnaire Short-Form (PMQ-SF) after each treatment [ Time Frame: Immediately after the interventions ]
    The Psychedelic Music Questionnaire Short-Form consists of 15 statements rated from 1 (none) to 5 (extremely). Possible scores range from 0 to 75 with higher scores indicating stronger engagement with, and appreciation of, the music experience.
  • Inflammatory markers before and after the first and last treatment [ Time Frame: Treatment 1 and 6 (day 23) ]
    Blood samples collected from subjects during the first and last treatments, before and after the infusions, totally 4 samples per patient. A panel of inflammatory markers (including interleukin-6, interleukin-1β, interleukin-1ra, interleukin-10, C-reactive protein) will be analyzed to evaluate treatment effects of one and six ketamine infusions in an exploratory fashion.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Music as an Intervention to Improve Hemodynamic Tolerability of Ketamine in Depression
Official Title  ICMJE Music as a Potential Intervention to Improve Hemodynamic Tolerability of Repetitive Sub-Anesthetic IV Ketamine Infusions in Bipolar and Unipolar Depression: A Pilot Study
Brief Summary The purpose of this study is to assess the impact of music on patients receiving a course of intravenous (IV) ketamine for treatment-resistant depression (TRD), both unipolar and bipolar. The primary outcome is changes in in systolic blood pressure throughout each 40-minute infusion. Secondary outcomes include repeated measures of mood, anxiety, suicidality, and psychological/physical pain. Aspects of the treatment experience, with and without music, will also be explored.
Detailed Description

Depression is the first cause of disability worldwide, and approximately 1 in 3 patients will fail to respond to current treatments. Intravenous (IV) low-dose ketamine has remarkable efficacy in even the most treatment-resistant depression (here defined as failure to at least two adequate trials of Level 1-evidence psychiatric medications), inducing remission in 25-50%.

Over 100 randomized clinical trials (RCTs) show that music can mitigate hemodynamic and psychological stress caused by even highly invasive medical procedures. Though never studied, music may similarly improve ketamine tolerability.

In this randomized, single-blind (assessors will not know whether participants receive music or not) single-center trial, 20 participants with TRD will receive 1) curated music or 2) no music during their course of 6 IV ketamine treatments (0.50mg/kg bodyweight) over 4 weeks. The primary aim is to compare changes in systolic blood pressure from the beginning to the end (40 minutes, peak plasma concentration) of each infusion between groups.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Masking Description:
The primary investigator and outcome assessors will be masked throughout the trial. Participants and clinicians administering the ketamine treatments will not be masked, given the nature of the music intervention.
Primary Purpose: Treatment
Condition  ICMJE
  • Depressive Disorder, Treatment-Resistant
  • Depressive Disorder, Major
  • Unipolar Depression
  • Depression, Bipolar
Intervention  ICMJE Other: Music
Music will be provided via headphones during all 6 ketamine treatments, beginning at the commencement of each infusion and ending 55 minutes later. On the day of each infusion, before the treatment begins, clinicians will discuss music choices with participants in order to select amongst one of several options that have been designed for this purpose (length, genre, intensity, etc.).
Study Arms  ICMJE
  • Experimental: Music
    Music will be provided for participant's six 40 minute IV infusions of 0.5mg/kg ketamine administered over four weeks (biweekly for 2 weeks, then weekly for 2 weeks).
    Intervention: Other: Music
  • No Intervention: Usual Care
    Participant's six 40 minute IV infusions of 0.5mg/kg ketamine administered over four weeks (biweekly for 2 weeks, then weekly for 2 weeks) will be administered as per usual care. That is, without music provided or permitted. Contact time with clinicians before, during, and after ketamine treatments will be matched.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 7, 2021)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Bipolar and unipolar depressive episode, current episode of depression (DSM-V) despite at least two adequate trials of Level 1-evidence psychiatric medications.
  • No active substance use disorder (beyond nicotine use disorder);
  • No contraindication of ketamine;
  • Not of childbearing potential, defined as: Postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL in the postmenopausal range) will be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
  • Permanently sterile: permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
  • Female subjects of childbearing potential must have a negative urine pregnancy test at the beginning and be willing to use a highly effective method of contraception during the treatment and after the last ketamine infusion.
  • Female subjects of childbearing potential must practice a highly effective method of contraception (failure rate of <1percent per year when used consistently and correctly) beginning at least two weeks before and continued while receiving ketamine infusions;
  • Male subjects who are sexually active with a woman of childbearing potential must agree to use a double-barrier method of contraception (eg, diaphragm or cervical/vault caps plus condom with spermicidal foam/gel/film/cream/suppository).
  • Male subjects who are sexually active with a woman who is pregnant must agree to use a condom. Male subjects must also agree to not donate sperm during the treatment and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of ketamine;
  • Abstention from consuming grapefruit juice (a potent 3A4 cytochrome inhibitor) on the day of the ketamine infusions as it may alter the metabolism of ketamine;
  • Provision of written informed consent after reading the participant information handout;

Exclusion Criteria:

  • Baseline blood pressure within normal limits, i.e. below 140/90 mmHg, when measured thrice in a quiet room.
  • Significant hearing impairment not improved with hearing aids and/or sound amplification or unwillingness to listen to music during treatment;
  • The subject's depressive symptoms have previously demonstrated non-response to esketamine or ketamine in the current major depressive episode;
  • Known intellectual deficiency or autism spectrum disorder;
  • Unable to accommodate regular visits to the Depressive Disorders Program at the Douglas Mental Health University Institute, Montreal, QC;
  • Depression evaluated as secondary to stroke, cancer or other severe medical illnesses;
  • Known risk factors for intracranial hemorrhage, including previous significant trauma, known aneurysm, or previous neurosurgery;
  • Evidence of clinically relevant disease, e.g., renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome;
  • Prior or current substance abuse or dependence (except for caffeine or nicotine dependence) and/or recent history (last 12 months) of alcohol or cannabis abuse or dependence, as defined by DSM-5 criteria. (Cannabis will be considered similarly to alcohol for the purpose of this study, as it is clinically, in the context of its legalization in Canada. That is, recreational use that does not meet criteria for a substance use disorder and/or is not deemed to be negatively impacting participants' physical and mental health will not justify exclusion from the study just as it does not justify exclusion from purely clinical treatment by ketamine.)
  • A positive toxicology screen for drugs that are not prescribed;
  • Unwilling, or unable to receive treating physician's agreement, or unable to hold benzodiazepines from the evening prior to the infusion of ketamine;
  • Unwilling, or unable to receive treating physician's agreement, to discontinue any narcotic beginning a minimum of 5 drug half-lives prior to infusion;
  • Unwilling, or unable to receive treating physician's agreement, to discontinue memantine (an NMDA antagonist) during infusions, beginning a minimum of 5 drug half-lives prior to infusions;
  • Pregnant, lactating, or of childbearing potential and not willing to use an approved method of contraception during the ketamine infusion, as per above;
  • A clinical finding that is unstable or that, in the opinion of the treating clinician(s), would be negatively affected by, or would affect, the medication (e.g., diabetes mellitus, unstable angina);
  • Liver function tests AST and ALT three times the upper normal limit at screening.
  • Uncorrected hypothyroidism or hyperthyroidism: Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 3 months prior to beginning infusions;
  • Clinically significant deviation from the reference range in clinical laboratory test results as judged by the clinician(s);
  • ECG results considered significantly abnormal as determined by the clinician(s);
  • History of seizure disorder, except febrile convulsions;
  • Known history of intolerance or hypersensitivity to ketamine;
  • Acute psychotic symptoms, as judged by the initial clinical interview or reported by referring clinicians;
  • Any significant, recent, acute decline in exercise tolerance.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kyle T Greenway, MD 514 377 3068 kyle.greenway@mail.mcgill.ca
Contact: Nicolas Garel, MD 514 699 3006 nicolas.garel@mail.mcgill.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04701866
Other Study ID Numbers  ICMJE DOUGKMT01
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  ICMJE Not Provided
Responsible Party Stéphane Richard-Devantoy, Douglas Mental Health University Institute
Study Sponsor  ICMJE Douglas Mental Health University Institute
Collaborators  ICMJE Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés
Investigators  ICMJE
Principal Investigator: Stéphane Richard-Devantoy, MD, PhD Douglas Mental Health University Insitute
PRS Account Douglas Mental Health University Institute
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP