Major Depressive DisorderPhase 4NCT02579928
Ketamine Infusion for Adolescent Depression and Anxiety
A Phase 4 study testing Ketamine and Midazolam in people with Major Depressive Disorder and Anxiety Disorder, run by Yale University at 2 sites in United States.
Trial summary
The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety disorder, panic disorder, generalized anxiety… Read more about this study
- Who is it for?
- Ages 13 to 17 years
- Conditions the study is for
- Major Depressive Disorder, Anxiety Disorder
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2015to Sep 2019
- Phase
- Phase 4
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 13 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- MDD Cohort:
- Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID)
- CDRS-R score >40.
- Failure to achieve remission with at least 1 adequate prior antidepressant trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.
- Anxiety Cohort:
- Meet DSM-5 criteria for any of the following anxiety disorders: Social Anxiety Disorders, Generalized Anxiety Disorder, Separation Anxiety Disorder and/or Panic Disorder by structured interview (MINI-KID)
Show all 13Show fewer
- ADIS Clinical Severity Rating ≥4 (moderately severe) for any of the 4 included anxiety disorders
- Failure to achieve remission with at least 1 adequate prior anxiolytic medication trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.
- Failure to achieve remission with previous CBT or subject declines current CBT therapy
- Both cohorts:
- Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy.
- Medically and neurologically healthy on the basis of physical examination and medical history.
- Parents able to provide written informed consent and adolescents must additionally provide assent.
Who cannot join
- Current inpatient hospitalization or active suicidal ideation requiring referral for inpatient hospitalization for safety.
- History of psychotic disorder or manic episode diagnosed by MINI-KID
- History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
- Pregnancy (urine pregnancy tests on the day of scans for menstruating girls).
- Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hospital Research Unit at the Yale New Haven Hospital
New Haven, Connecticut, 06510
Yale Child Study Center
New Haven, Connecticut, 06520
About this study
Official title: Efficacy of Rapid-Acting NMDA Antagonist for Treatment of Adolescent Depression and Anxiety Disorders
The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety disorder, panic disorder, generalized anxiety disorder and/or separation anxiety disorder).
Read the detailed description
We will conduct a crossover trial in which as many as 36 adolescents (18 with MDD and 18 with anxiety disorders) will be given a single infusion of ketamine (study drug) or midazolam (active control). MDD symptoms and anxiety symptoms will be monitored over a two-week period. If applicable, comorbid school refusal symptoms will also be monitored over a two-week period for both cohorts. A 2-week washout period will be required between infusion doses. Our primary outcomes will be 1) improvement in MDD symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial and 2) improvement in the anxiety symptoms (measured by the Multimodal Anxiety Scale for Children (MASC) acute physical symptoms subscale) for the cohort of subjects enrolled in the anxiety disorders arm of the trial.
- Conditions
- Major Depressive Disorder, Anxiety Disorder
- Keywords
- Ketamine, Depression, Major Depressive Disorder, Anxiety, School refusal, Suicide, Generalized Anxiety, Suicidal Ideation
- Medical subject headings
- Depressive Disorder, Major, Anxiety Disorders, Depression, Phobia, School, Suicide, Generalized Anxiety Disorder, Suicidal Ideation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
A single dose of 0.5mg/kg of Ketamine will be administered Intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.
MidazolamDrug
Also called Versed
A single dose of 0.045mg/kg of Midazolam will be administered intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants were randomly be assigned to receive a dose of 0.5 mg/kg of Ketamine (administered intravenously over 40 minutes with a maximum total dose allowed in this study will be 50mg). Receives: Drug: Ketamine |
| Midazolam | Experimental | Participants were randomly assigned to receive a dose of 0.045mg/kg of Midazolam (administered Intravenously over 40 minutes with a the maximum total dose allowed in this study of 4.5mg), Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion
Depressive symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) on 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial.
Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
Usual cutoff points are:
0 to 6 - normal /symptom absent. 7 to 19 - mild depression. 20 to 34 - moderate depression. >34 - severe depression.
Measured: 1 day after the infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study startOct 2015
- Primary completion28 Sep 2018
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants were randomly assigned the treatment order, with participants receiving a single infusion of either ketamine hydrochloride (0.5 mg/kg) or midazolam (0.045 mg/kg) on Day 1, and the alternate compound 2 weeks later.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- American Academy of Child Adolescent Psychiatry.
- Responsible party
- Sponsor
- Investigators
- Michael H. Bloch, MD MS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579928
- Sponsor's protocol ID
- 1506016041
- Status last verified
- Jun 2020
- First submitted
- 16 Oct 2015
- Last updated
- 14 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.
PubMed 8122957Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.
PubMed 10686270Zarate 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.
PubMed 16894061Niciu MJ, Ionescu DF, Richards EM, Zarate CA Jr. Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm (Vienna). 2014 Aug;121(8):907-24. doi: 10.1007/s00702-013-1130-x. Epub 2013 Dec 8.
PubMed 24318540Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsche NE, Ameli R, Furey ML, Zarate CA Jr. Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res. 2014 Nov;58:161-6. doi: 10.1016/j.jpsychires.2014.07.027. Epub 2014 Aug 12.
PubMed 25169854Lineham A, Avila-Quintero VJ, Bloch MH, Dwyer J. Exploring Predictors of Ketamine Response in Adolescent Treatment-Resistant Depression. J Child Adolesc Psychopharmacol. 2024 Mar;34(2):73-79. doi: 10.1089/cap.2023.0047. Epub 2024 Jan 3.
PubMed 38170185Lineham A, Avila-Quintero VJ, Bloch MH, Dwyer J. The Relationship Between Acute Dissociative Effects Induced by Ketamine and Treatment Response in Adolescent Patients with Treatment-Resistant Depression. J Child Adolesc Psychopharmacol. 2023 Feb;33(1):20-26. doi: 10.1089/cap.2022.0086.
PubMed 36799961