A Single Ketamine Infusion Combined With Music for Suicidal Ideation

NCT04658420 | Unknown Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-042KL2TR003168
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Suicidal ideation (SI) associated with major and bipolar depression is commonly seen in a wide range of clinical practice situations including the emergency room (ER). Current treatment regimens are often unsatisfactory. About a third of patients fail to respond to currently available therapy, and there are no currently FDA indicated rapid acting treatments for SI. Suboptimal outcomes have triggered the search for new, well-tolerated and more effective forms of treatment. Small clinical trials suggest that low dose (0.5mg/kg) ketamine is safe and effective for SI. We believe adding music during ketamine infusion may reduce anxiety and lead to more reduced SI based on available evidence. We are testing the hypothesis that a single infusion of ketamine combined with music enhances tolerability and improves outcomes in the treatment of SI when combined with treatment as usual in a factorial study design. One treatment with Ketamine + music will be compared to compared to one-time treatment with ketamine alone, music alone, or treatment as usual. 50 individuals with a depressive episode and suicidal ideation will receive intravenous (IV) ketamine 0.5mg/kg infused over 40 minutes once with 60 minutes of music, 50 individuals will receive IV ketamine without music, 50 subjects will receive 60 minutes of music once, and 50 patients will receive treatment as usual without ketamine or music. We anticipate that the ketamine + music group will have statistically significant indices of improvement in the primary outcome, suicidal ideation scores on the Scale for Suicidal Ideation (SSI) 4 weeks after the ketamine infusion. Secondary outcomes will include depression scores on the MontgomeryÅsberg Depression Rating Scale (MADRS) scale, adverse effects, and SSI scores at the end of 4 weeks. If, as we anticipate, the results indicate success of ketamine + music for SI, the work will identify new opportunities to more effectively manage patients with depression and suicidal ideation presenting to the ER.

Conditions

Suicidal Ideation; Depressive Episode

Outcome Measures

Primary Outcomes (1)

• Scale for Suicide Ideation (SSI)

  Clinician administered scale. Score range 0-38. Higher scores are indicative of increased suicidal ideation. The primary efficacy evaluation for each panel will be the change in SSI total score from baseline, prior to the first IV ketamine dose, to 4 weeks after IV ketamine treatment. 25 % reduction in score will be deemed treatment response, 50% reduction will be determined to be treatment remission.

  4 weeks

Secondary Outcomes (4)

• Montgomery Asberg Depression Rating Scale (MADRS)

  4 weeks

• World Health Organization Quality of life Scale (WHOQOL-BREF)

  4 weeks

• Quick Inventory of Depressive Symptomatology (QIDS SR-16)

  4 weeks

• Time of hospitalization

  4 weeks

Study Arms (4)

Ketamine

EXPERIMENTAL

One group will receive IV ketamine 0.5mg/kg infused over forty minutes

Drug: Ketamine Hydrochloride

Ketamine + Music

EXPERIMENTAL

One group will receive IV ketamine 0.5mg/kg infused over forty minutes with one hour of pre-planned music

Drug: Ketamine Hydrochloride; Other: Music

Music

EXPERIMENTAL

One hour of pre-planned music without ketamine

Other: Music

Treatment as usual

NO INTERVENTION

No music nor ketamine given

Interventions

Ketamine Hydrochloride DRUG

Individuals in the ketamine group will receive ketamine 0.5 mg/kg infused over 40 minutes

Also known as: Ketamine

Ketamine; Ketamine + Music

Music OTHER

A playlist by composer Nils Frahm will be played for 60 minutes. The music is instrumental, relaxing and subjectively thought to be uplifting by patients who have listened to the music during ketamine infusions performed previously by the PI for treatment of resistant depression. Music can be previewed at the link below: https://open.spotify.com/playlist/37i9dQZF1DWVbGPBkXJYHF

Ketamine + Music; Music

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults age 18-64
• DSM-IV diagnosis of depressive episode as determined by the Mini International neuropsychiatric Interview criteria, and Montgomery Asberg Depression Rating Scale ≥ 28
• Suicidal ideation at baseline as and positive suicidal ideation defined as Scale for Suicidal Ideation score ≥4.
• Diagnosis of Major depressive disorder, bipolar disorder, or substance induced mood disorder will be included.

You may not qualify if:

• Active psychotic symptoms
• Current manic episode
• Previous diagnosis of Schizophrenia or Schizoaffective disorder
• Previous diagnosis of Intellectual disability or Autism Spectrum Disorder
• Previous diagnosis of Major Neurocognitive Disorder
• History of ketamine abuse or dependence
• Hypersensitivity to esketamine, ketamine, or any of the excipients.
• Uncontrolled clinically significant medical conditions such as:
• Respiratory illness requiring the use of oxygen
• Previously documented prolonged QTc interval
• Current Aneurysmal vascular disease
• Arteriovenous malformation
• Intracerebral hemorrhage
• Unstable cardiac disease including history of myocardial infarction
• Positive urine pregnancy test

Sponsors & Collaborators

• The University of Texas Health Science Center at Tyler: lead
• National Institutes of Health (NIH): collaborator
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (1)

UT Health East Texas

Tyler, Texas, 75703, United States

Location

Related Publications (16)

• Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003 Apr 15;53(8):649-59. doi: 10.1016/s0006-3223(03)00231-2.

  PMID: 12706951 BACKGROUND

• Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

  PMID: 17074942 BACKGROUND

• Grunebaum MF, Ellis SP, Keilp JG, Moitra VK, Cooper TB, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Bipolar Disord. 2017 May;19(3):176-183. doi: 10.1111/bdi.12487. Epub 2017 Apr 28.

  PMID: 28452409 BACKGROUND

• aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):139-45. doi: 10.1016/j.biopsych.2009.08.038.

  PMID: 19897179 BACKGROUND

• Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, Sos P, Wang G, Zarate CA Jr, Sanacora G. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018 Feb 1;175(2):150-158. doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3.

  PMID: 28969441 BACKGROUND

• Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5.

  PMID: 29202655 BACKGROUND

• George D, Galvez V, Martin D, Kumar D, Leyden J, Hadzi-Pavlovic D, Harper S, Brodaty H, Glue P, Taylor R, Mitchell PB, Loo CK. Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression. Am J Geriatr Psychiatry. 2017 Nov;25(11):1199-1209. doi: 10.1016/j.jagp.2017.06.007. Epub 2017 Jun 13.

  PMID: 28739263 BACKGROUND

• Aalbers S, Fusar-Poli L, Freeman RE, Spreen M, Ket JC, Vink AC, Maratos A, Crawford M, Chen XJ, Gold C. Music therapy for depression. Cochrane Database Syst Rev. 2017 Nov 16;11(11):CD004517. doi: 10.1002/14651858.CD004517.pub3.

  PMID: 29144545 BACKGROUND

• Bradt J, Dileo C, Shim M. Music interventions for preoperative anxiety. Cochrane Database Syst Rev. 2013 Jun 6;2013(6):CD006908. doi: 10.1002/14651858.CD006908.pub2.

  PMID: 23740695 BACKGROUND

• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

  PMID: 24740528 BACKGROUND

• Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018 Jun;5(6):486-497. doi: 10.1016/S2215-0366(18)30135-4. Epub 2018 May 1.

  PMID: 29728331 BACKGROUND

• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

  PMID: 27210031 BACKGROUND

• Albott CS, Lim KO, Forbes MK, Erbes C, Tye SJ, Grabowski JG, Thuras P, Batres-Y-Carr TM, Wels J, Shiroma PR. Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. J Clin Psychiatry. 2018 May/Jun;79(3):17m11634. doi: 10.4088/JCP.17m11634.

  PMID: 29727073 BACKGROUND

• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.

  PMID: 9881538 BACKGROUND

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

  PMID: 444788 BACKGROUND

• Beck AT, Kovacs M, Weissman A. Assessment of suicidal intention: the Scale for Suicide Ideation. J Consult Clin Psychol. 1979 Apr;47(2):343-52. doi: 10.1037//0022-006x.47.2.343. No abstract available.

  PMID: 469082 BACKGROUND

Related Links

• The Underlying Cause of Death database contains mortality and population counts for all U.S. counties. Data are based on death certificates for U.S. residents.
• Smith county Suicide rates

MeSH Terms

Conditions

Suicidal Ideation

Interventions

Ketamine; Music Therapy

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Sensory Art Therapies; Complementary Therapies; Therapeutics; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Richard Idell, MD

  University of Texas Health Science Center at Tyler

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Idell, MD

CONTACT

2816088348; richard.idell@uthct.edu

Connie Castleberry, RN

CONTACT

9038775455; connie.castleberry@uthct.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All four groups will receive treatment as usual as defined above (potential approved hospitalization, medication, psychotherapy, outpatient referrals, suicide safety planning). A factorial design is being implemented to test four interventions. One group will receive IV ketamine 0.5mg/kg infused over forty minutes with one hour of pre-planned music will be compared to 3 other groups: One group will receive the same dose of ketamine without music, one group will one hour of music without ketamine, and one group will receive neither music nor ketamine. During the 4-week follow up interval, subjects from both groups will be contacted by phone for weekly assessment of depression, SI and quality of life.

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: December 8, 2020
• Study Start: July 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: April 1, 2023
• Last Updated: May 7, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)