Depressive Disorder, Treatment-ResistantNCT04701866

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

A study testing Music in people with Depressive Disorder, Treatment-Resistant and Depressive Disorder, Major, run by Douglas Mental Health University Institute at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Unipolar Depression
What is being tested?: Music
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 2 sitesCanada
Study dates: 11 Jan 2021to 24 Aug 2022
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 11Show fewer

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;

Who cannot join

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;

Show all 23Show fewer

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.

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

Jewish General Hospital
Montreal, Quebec, H3T 1E2
Douglas Mental Health University Institute
Montreal, Quebec, H4H 1R3

Other trials in Canada

About this study

Official title: Music as a Potential Intervention to Improve Hemodynamic Tolerability of Repetitive Sub-Anesthetic IV Ketamine Infusions in Bipolar and Unipolar Depression: A Pilot Study

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.

Read the 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.

Conditions: Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Unipolar Depression, Depression, Bipolar
Being tested: Music
Keywords: Treatment-Resistant Depression, Ketamine, Music, Hemodynamic Changes
Medical subject headings: Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Depressive Disorder, Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MusicOther
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 groups in NCT04701866
Study group	Role	What they receive
Music	Experimental	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). Receives: Other: Music
Usual Care	No intervention	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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Changes in Systolic Blood Pressure
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.
Measured: From 0 to 40 minutes of each infusion.

Secondary outcomes (25)

Change From Baseline in MADRS Total Score to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in MADRS Total Score to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Improvement Score to Last Treatment
The Clinician-Rated Global Impression Improvement score (CGI-I) rates improvement with treatment from 1 to 7, with higher scores indicating a worse outcome.
Measured: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Severity Score to Last Treatment
The Clinician-Rated Global Impression Severity score (CGI-S) rates severity of illness from 1 to 7, with higher scores indicating a worse outcome.
Measured: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Improvement Score to Follow-up
The Clinician-Rated Global Impression Improvement score (CGI-I) rates improvement with treatment from 1 to 7, with higher scores indicating a worse outcome.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Severity Score to Follow-up
The Clinician-Rated Global Impression Severity score (CGI-S) rates severity of illness from 1 to 7, with higher scores indicating a worse outcome.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in PSQI Total and Subscores to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in PSQI Total and Subscores to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Psychological and Physical Pain to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in Psychological and Physical Pain to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y A to Last Treatment
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.
Measured: Baseline, Day 23
Change From Baseline in STAI-Y A to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y B to Last Treatment
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.
Measured: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y B to Follow-up
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.
Measured: Baseline, 1-month follow-up (8 weeks)
The Mystical Experience Questionnaire (MEQ) after each treatment
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.
Measured: Immediately after the interventions
The Psychedelic Music Questionnaire Short-Form (PMQ-SF) after each treatment
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.
Measured: Immediately after the interventions
Inflammatory markers before and after the first and last treatment
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.
Measured: Treatment 1 and 6 (day 23)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jan 202124 Aug 2022

First posted8 Jan 2021
Study start11 Jan 2021
Primary completion24 Aug 2022
Study completion24 Aug 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (25)Papers the sponsor has linked to this study.
Other trials for Depressive Disorder, Treatment-ResistantStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Investigator, Outcomes assessor
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04701866
Sponsor's protocol ID: DOUGKMT01
Status last verified: Oct 2022
First submitted: 4 Jan 2021
Last updated: 4 Oct 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Weinberger AH, Gbedemah M, Martinez AM, Nash D, Galea S, Goodwin RD. Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups. Psychol Med. 2018 Jun;48(8):1308-1315. doi: 10.1017/S0033291717002781. Epub 2017 Oct 12.
PubMed 29021005
Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019 Feb 1;22(2):85-92. doi: 10.1093/ijnp/pyy052.
PubMed 29961822
Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013 May 11;381(9878):1672-82. doi: 10.1016/S0140-6736(13)60857-0.
PubMed 23663953
Pompili M, Gonda X, Serafini G, Innamorati M, Sher L, Amore M, Rihmer Z, Girardi P. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013 Aug;15(5):457-90. doi: 10.1111/bdi.12087. Epub 2013 Jun 12.
PubMed 23755739
Grady SE, Marsh TA, Tenhouse A, Klein K. Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature. Ment Health Clin. 2018 Mar 23;7(1):16-23. doi: 10.9740/mhc.2017.01.016. eCollection 2017 Jan.
PubMed 29955493
Fukumoto K, Fogaca MV, Liu RJ, Duman C, Kato T, Li XY, Duman RS. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):297-302. doi: 10.1073/pnas.1814709116. Epub 2018 Dec 17.
PubMed 30559184
De Kock M, Loix S, Lavand'homme P. Ketamine and peripheral inflammation. CNS Neurosci Ther. 2013 Jun;19(6):403-10. doi: 10.1111/cns.12104. Epub 2013 Apr 10.
PubMed 23574634
Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study. Psychiatry Res. 2018 Nov;269:207-211. doi: 10.1016/j.psychres.2018.08.078. Epub 2018 Aug 21.
PubMed 30153598
Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
PubMed 25271445
van Schalkwyk GI, Wilkinson ST, Davidson L, Silverman WK, Sanacora G. Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale. J Affect Disord. 2018 Feb;227:11-16. doi: 10.1016/j.jad.2017.09.023. Epub 2017 Sep 28.
PubMed 29045915
Conrad C, Niess H, Jauch KW, Bruns CJ, Hartl W, Welker L. Overture for growth hormone: requiem for interleukin-6? Crit Care Med. 2007 Dec;35(12):2709-13. doi: 10.1097/01.ccm.0000291648.99043.b9.
PubMed 18074473
Wiwatwongwana D, Vichitvejpaisal P, Thaikruea L, Klaphajone J, Tantong A, Wiwatwongwana A; Medscape. The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial. Eye (Lond). 2016 Nov;30(11):1407-1414. doi: 10.1038/eye.2016.160. Epub 2016 Oct 14.
PubMed 27740618
Merakou K, Varouxi G, Barbouni A, Antoniadou E, Karageorgos G, Theodoridis D, Koutsouri A, Kourea-Kremastinou J. Blood Pressure and Heart Rate Alterations through Music in Patients Undergoing Cataract Surgery in Greece. Ophthalmol Eye Dis. 2015 Jun 11;7:7-12. doi: 10.4137/OED.S20960. eCollection 2015.
PubMed 26106264
Bradt J, Dileo C. Music interventions for mechanically ventilated patients. Cochrane Database Syst Rev. 2014;2014(12):CD006902. doi: 10.1002/14651858.CD006902.pub3. Epub 2014 Dec 9.
PubMed 25490233
Metcalf CS, Huntsman M, Garcia G, Kochanski AK, Chikinda M, Watanabe E, Underwood T, Vanegas F, Smith MD, White HS, Bulaj G. Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs. Front Neurol. 2019 Mar 27;10:277. doi: 10.3389/fneur.2019.00277. eCollection 2019.
PubMed 30972009

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Music as a Potential Intervention to Improve Hemodynamic Tolerability of Repetitive Sub-Anesthetic IV Ketamine Infusions in Bipolar and Unipolar Depression: A Pilot Study
ClinicalTrials.gov ID: NCT04701866
Acronym / sponsor ID: DOUGKMT01
Conditions: Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Unipolar Depression, Depression, Bipolar
Keywords: Treatment-Resistant Depression, Ketamine, Music, Hemodynamic Changes
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Douglas Mental Health University InstituteUniversity, hospital or other
Collaborators: Réseau québécois sur le suicide, les troubles de l'humeur et les troubles associés
Study start: 11 Jan 2021 (actual)
Primary completion: 24 Aug 2022 (actual)
Study completion: 24 Aug 2022 (actual)
First posted: 8 Jan 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Music	Experimental	Other: MusicMusic 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).
Usual Care	No intervention	–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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (23 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MusicMusic 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.).	Other	Music

Primary outcome

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.

25 secondary outcomes

Change From Baseline in MADRS Total Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in MADRS Total Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Beck Depression Inventory (BDI-II) Total Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Improvement Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Severity Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Clinician-Rated Global Impression Improvement Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Severity Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Suicidality Severity Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Clinician-Rated Global Impression Suicidality Improvement Score to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in PSQI Total and Subscores to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in PSQI Total and Subscores to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Beck Scale for Suicide Ideation (SSI) Total to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in Psychological and Physical Pain to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in Psychological and Physical Pain to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y A to Last Treatment
Time frame: Baseline, Day 23
Change From Baseline in STAI-Y A to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y B to Last Treatment
Time frame: Baseline, 1-month follow-up (8 weeks)
Change From Baseline in STAI-Y B to Follow-up
Time frame: Baseline, 1-month follow-up (8 weeks)
The Mystical Experience Questionnaire (MEQ) after each treatment
Time frame: Immediately after the interventions
The Psychedelic Music Questionnaire Short-Form (PMQ-SF) after each treatment
Time frame: Immediately after the interventions
Inflammatory markers before and after the first and last treatment
Time frame: Treatment 1 and 6 (day 23)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
Background: PubMed 29021005Weinberger AH, Gbedemah M, Martinez AM, Nash D, Galea S, Goodwin RD. Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups. Psychol Med. 2018 Jun;48(8):1308-1315. doi: 10.1017/S0033291717002781. Epub 2017 Oct 12.
Background: PubMed 29961822Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019 Feb 1;22(2):85-92. doi: 10.1093/ijnp/pyy052.
Background: PubMed 23663953Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013 May 11;381(9878):1672-82. doi: 10.1016/S0140-6736(13)60857-0.
Background: PubMed 23755739Pompili M, Gonda X, Serafini G, Innamorati M, Sher L, Amore M, Rihmer Z, Girardi P. Epidemiology of suicide in bipolar disorders: a systematic review of the literature. Bipolar Disord. 2013 Aug;15(5):457-90. doi: 10.1111/bdi.12087. Epub 2013 Jun 12.
Background: PubMed 29955493Grady SE, Marsh TA, Tenhouse A, Klein K. Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature. Ment Health Clin. 2018 Mar 23;7(1):16-23. doi: 10.9740/mhc.2017.01.016. eCollection 2017 Jan.
Background: PubMed 30559184Fukumoto K, Fogaca MV, Liu RJ, Duman C, Kato T, Li XY, Duman RS. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):297-302. doi: 10.1073/pnas.1814709116. Epub 2018 Dec 17.
Background: PubMed 23574634De Kock M, Loix S, Lavand'homme P. Ketamine and peripheral inflammation. CNS Neurosci Ther. 2013 Jun;19(6):403-10. doi: 10.1111/cns.12104. Epub 2013 Apr 10.
Background: PubMed 30153598Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study. Psychiatry Res. 2018 Nov;269:207-211. doi: 10.1016/j.psychres.2018.08.078. Epub 2018 Aug 21.
Background: PubMed 25271445Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.
Background: PubMed 29045915van Schalkwyk GI, Wilkinson ST, Davidson L, Silverman WK, Sanacora G. Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale. J Affect Disord. 2018 Feb;227:11-16. doi: 10.1016/j.jad.2017.09.023. Epub 2017 Sep 28.
Background: PubMed 18074473Conrad C, Niess H, Jauch KW, Bruns CJ, Hartl W, Welker L. Overture for growth hormone: requiem for interleukin-6? Crit Care Med. 2007 Dec;35(12):2709-13. doi: 10.1097/01.ccm.0000291648.99043.b9.
Background: PubMed 27740618Wiwatwongwana D, Vichitvejpaisal P, Thaikruea L, Klaphajone J, Tantong A, Wiwatwongwana A; Medscape. The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial. Eye (Lond). 2016 Nov;30(11):1407-1414. doi: 10.1038/eye.2016.160. Epub 2016 Oct 14.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stéphane Richard-Devantoy, MD, PhD principal investigator

Douglas Mental Health University Insitute

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Music in people with Depressive Disorder, Treatment-Resistant and Depressive Disorder, Major, run by Douglas Mental Health University Institute at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in Systolic Blood Pressure (time frame: From 0 to 40 minutes of each infusion.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04701866, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.