Depressive DisorderPhase 4KETProjectNCT04234776

Intramuscular Ketamine Versus Aripiprazole and Escitalopram in the Treatment of Resistant Depression

A Phase 4 study testing Ketamine, Cognition and Suicide risk in people with Depressive Disorder, run by University of Sao Paulo at 1 site in Brazil.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages 18 to 40 years
Conditions the study is for: Depressive Disorder
What is being tested?: Ketamine, Cognition and Suicide risk
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 88 participants
Where: 1 siteBrazil
Study dates: 3 Apr 2018to 3 Apr 2021
Phase: Phase 4
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 40 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
Moderate to severe intensity of the disease;
Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
Literate and able to understand the tasks requested;
With clinical comorbidities, however compensated;
Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.

Who cannot join

Imminent risk of suicide;
Patients with psychoactive substance dependence;
Intellectual deficit and psychotic symptoms;
Bipolar spectrum disorders and other primary psychiatric diagnoses;
Allergic to ketamine;
Glaucoma;

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Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
Treatment with irreversible MAOI in two weeks prior to visit 0;
Fluoxetine treatment within 4 weeks prior to visit 0;
Treatment with others antidepressants;
Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
Lorazepam and zolpidem may be used;
Patients who become pregnant will be excluded from the study and referred for obstetric care.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

Núcleo de Pesquisas em Saúde Mental
Blumenau, Santa Catarina, 89.020-070

Other trials in Brazil

About this study

Official title: Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression

The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.

Read the detailed description

Compare the response of ketamine IM versus active control in treatment-resistant depression (TRD [primary outcome]) and find safety and tolerability of ketamine IM, evaluate changes in life quality, cognition and suicidal risk (secondary outcomes)

Conditions: Depressive Disorder
Being tested: Ketamine, Cognition, Suicide risk, Depression thoughts, Quality of life and disability
Keywords: Ketamine, Treatment Resistant Depression
Medical subject headings: Depressive Disorder, Depressive Disorder, Treatment-Resistant

What participants receive

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

KetamineDrug
Also called Active comparator (escitalopram plus aripiprazole), Placebo
(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole
CognitionDiagnostic test
Composite tools
Suicide riskOther
MADRS (10) and HAM-D (3)
Depression thoughtsOther
EPD
Quality of life and disabilityOther
Quality of life and disability
Clinical and epidemiological factorsOther
Variables and categories
Safety of ketamine IMDevice
Vital signs
Tolerability of ketamine IMOther
UKU-SERS, YOUNG, CADSS and BPRS-12.

Study groups in NCT04234776
Study group	Role	What they receive
Rapid-acting antidepressant	Experimental	Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized. Receives: Drug: Ketamine; Diagnostic Test: Cognition; Other: Suicide risk; Other: Depression thoughts; Other: Quality of life and disability; Other: Clinical and epidemiological factors; Device: Safety of ketamine IM; Other: Tolerability of ketamine IM
Comparator	Active comparator	Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized Receives: Drug: Ketamine; Diagnostic Test: Cognition; Other: Suicide risk; Other: Depression thoughts; Other: Quality of life and disability; Other: Clinical and epidemiological factors; Device: Safety of ketamine IM; Other: Tolerability of ketamine IM

What is being measured

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

Change in depressive symptoms
Montomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and < 50% Response: MADRS ≥ 50% Remission: MADRS ≤10
Measured: 3 times a week in once month (Phase II)
Change in depressive symptoms
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)
Measured: Once a week in six months (Phase III)
Change in depressive symptoms
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome).
Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).
Measured: Once a week in once month (Phase IV)

Secondary outcomes (46)

Depression symptoms
Hamiltom Depression Ratins Scale (HAM-D [0-50] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
Clinical impressions-S
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
Clinical impressions-I
Clinical Global Impression Scale (CGI [0-7] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
Electrocardiographic monitoring
P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval and U wave Rhythm (irregular rhythm: worse outcome).
Measured: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Blood Pressure (BP [mmHg]).
BP low <90/60 (systolic/diastolic) mmHg and high >140/90 mmHg ( (systolic/diastolic).
Measured: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Heart rate (HR [bpm]).
Anormal HR <60 bpm or >100 bpm.
Measured: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Digital pulse oximetry (%).
Low oxygen saturation <95%.
Measured: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Respiratory rate (RR [cycles/min])
Anormal RR <10 cycles/min or >20 cycles/min.
Measured: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Suicide risk 1
Montgomery-Åsberg Depression Rating Scale (item 10 [0-6] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
Suicide risk 2
Hamilton Depression Rating Scale (item 3 [0-4] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
General side effects
Ugvalg for Kliniske Undersgelser-Side Effect Rating Scale (UKU-SERS [48 specific symptoms).
Measured: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Hypo/maniac symptoms
Young Mania Rating Scale (YOUNG [0-58] higher scores: worse outcome).
Measured: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Dissociative symptoms
Clinician-Administered Dissociative State Scale (CADSS [0-108] higher scores: worse outcome)
Measured: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Psychotic symptoms
Brief Psychiatric Rating Scale (item 12 [0-6] higher scores: worse outcome).
Measured: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Depression thoughts
Depression Thoughts Scale (EPD [1-78] higher scores: worse outcome)
Measured: Through study completion, an average of 1 year.
Stimate intelligence quocient
Wechsler Abreviated Scale of Intelligence (WASI [70-160 percentille] higher scores: better outcomes).
Measured: Through study completion, an average of 1 year.
Intelligence quocient
Wechsler Scale of Intelligence (WAIS III [70-155 percentille] higher scores: better outcomes).
Measured: Through study completion, an average of 1 year.
Attention
Trial Making Test (5-95 percentille, higher scores: better outcomes).
Measured: Through study completion, an average of 1 year.
Memory
Rey figures (10-100 percentille, higher scores: better outcomes)
Measured: Through study completion, an average of 1 year.
Executive functions 1
Wisconsin Test (50->80 score, higher scores: better outcomes).
Measured: Through study completion, an average of 1 year.
Executive functions 2
Stroop Color Word Test (5-95 percentille, higher scores: better outcomes)
Measured: Through study completion, an average of 1 year.
Verbal fluency 1
Verbal Fluency Test (FAS [10-90 percentille], higher scores: better outcomes))
Measured: Through study completion, an average of 1 year.
Verbal fluency 2
The Rey Auditory-Verbal Learning Test (RAVLT [5-95 percentille], higher scores: better outcomes).
Measured: Through study completion, an average of 1 year.
Functional recovery 1
World Health Organization Quality of Life (WHOQOL-brief [4 domains, 26 questions higher scores: better outcome]).
Measured: Through study completion, an average of 1 year.
Functional recovery 2
Sheehan Disability Scale (SDS [0-30] higher scores: worse outcome).
Measured: Through study completion, an average of 1 year.
Body Mass Index (BMI)
Weight and height (kg/m2).
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 1
Disease intensity (HAM-D [% of patients], moderate or severe)
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 2
Number of episodes (questionnaire [incidence])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 3
Current episode duration (questionnaire [years])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 4
Suicide attempts (questionnaire [% of pacients])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 5
History of physical abuse (questionnaire [% of pacients])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 6
History of sexual abuse (questionnaire [% of pacients])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 7
Psychiatric hospitalizations (questionnaire [% of pacients])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 8
Clinical comorbidities (questionnaire [% of patients]).
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 9
Family history of depression (questionnaire [% of patients])
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 10
Family history of bipolar disorders (questionnaire [% of patients)
Measured: Through study completion, an average of 1 year.
Clinical and psychiatric features 11
Family history of other mental disorders (questionnaire [% of patients]).
Measured: Through study completion, an average of 1 year.
Epidemiological features 1
Age (questionnaire [years]).
Measured: Through study completion, an average of 1 year.
Epidemiological features 2
Gender (questionnaire [% of patients]; male/female)
Measured: Through study completion, an average of 1 year.
Epidemiological features 3
Marital status (questionnaire [% of patients] single, married, separated, divorced or widower).
Measured: Through study completion, an average of 1 year.
Epidemiological features 4
Ethnicity (questionnaire [% of patients])
Measured: Through study completion, an average of 1 year.
Epidemiological features 5
Religion (questionnaire [% of patients] protestant, pentecostal or neopentecostal, spiritism, afro-brazilian, no religion or atheism and others]).
Measured: Through study completion, an average of 1 year.
Epidemiological features 6
Occupation (questionnaire [% of patients])
Measured: Through study completion, an average of 1 year.
Epidemiological features 7
Education (questionnaire [years])
Measured: Through study completion, an average of 1 year.
Epidemiological features 8
Individual income (questionnaire [dollars]).
Measured: Through study completion, an average of 1 year.
Epidemiological features 9
Family income (questionnaire [dollars]).
Measured: Through study completion, an average of 1 year.

Timeline

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

3 Apr 20183 Apr 2021

First posted21 Jan 2020
Study start3 Apr 2018
Primary completion3 Jun 2020 (estimated)
Study completion3 Apr 2021 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (47)Papers the sponsor has linked to this study.
Other trials for Depressive DisorderStudies of the same condition, open and under way.
More trials run by University of Sao PauloThe 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: Parallel groups
Model description: Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 88 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04234776
Sponsor's protocol ID: rampty2805
Acronym: KETProject
Status last verified: Dec 2019
First submitted: 7 Oct 2019
Last updated: 21 Jan 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 17074942
Bennabi D, Aouizerate B, El-Hage W, Doumy O, Moliere F, Courtet P, Nieto I, Bellivier F, Bubrovsky M, Vaiva G, Holztmann J, Bougerol T, Richieri R, Lancon C, Camus V, Saba G, Haesbaert F, d'Amato T, Charpeaud T, Llorca PM, Leboyer M, Haffen E. Risk factors for treatment resistance in unipolar depression: a systematic review. J Affect Disord. 2015 Jan 15;171:137-41. doi: 10.1016/j.jad.2014.09.020. Epub 2014 Oct 8.
PubMed 25305428
Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
PubMed 20151847
Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2.
PubMed 27486148
Saveanu R, Etkin A, Duchemin AM, Goldstein-Piekarski A, Gyurak A, Debattista C, Schatzberg AF, Sood S, Day CV, Palmer DM, Rekshan WR, Gordon E, Rush AJ, Williams LM. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment. J Psychiatr Res. 2015 Feb;61:1-12. doi: 10.1016/j.jpsychires.2014.12.018. Epub 2014 Dec 31.
PubMed 25586212
Perlis RH. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biol Psychiatry. 2013 Jul 1;74(1):7-14. doi: 10.1016/j.biopsych.2012.12.007. Epub 2013 Feb 4.
PubMed 23380715
McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS, Barakat M, Miguelez M. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014 Mar;156:1-7. doi: 10.1016/j.jad.2013.10.043. Epub 2013 Nov 15.
PubMed 24314926
Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403. doi: 10.1371/journal.pmed.1001403. Epub 2013 Mar 12.
PubMed 23554581
Millan MJ, Goodwin GM, Meyer-Lindenberg A, Ove Ogren S. Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 2015 May;25(5):599-656. doi: 10.1016/j.euroneuro.2015.01.016. Epub 2015 Feb 7.
PubMed 25836356
Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, Vos T, Whiteford HA. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. Epub 2013 Nov 5.
PubMed 24223526
GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6.
PubMed 27733282
Machado MO, Veronese N, Sanches M, Stubbs B, Koyanagi A, Thompson T, Tzoulaki I, Solmi M, Vancampfort D, Schuch FB, Maes M, Fava GA, Ioannidis JPA, Carvalho AF. The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med. 2018 Jul 20;16(1):112. doi: 10.1186/s12916-018-1101-z.
PubMed 30025524
Evans-Lacko S, Knapp M. Global patterns of workplace productivity for people with depression: absenteeism and presenteeism costs across eight diverse countries. Soc Psychiatry Psychiatr Epidemiol. 2016 Nov;51(11):1525-1537. doi: 10.1007/s00127-016-1278-4. Epub 2016 Sep 26.
PubMed 27667656
Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059.
PubMed 24789696
Lepine BA, Moreno RA, Campos RN, Couttolenc BF. Treatment-resistant depression increases health costs and resource utilization. Braz J Psychiatry. 2012 Dec;34(4):379-88. doi: 10.1016/j.rbp.2012.05.009.
PubMed 23429808

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 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Intramuscular Ketamine Versus Escitalopram and Aripiprazole in Acute and Maintenance Treatment of Patients With Treatment-resistant Depression
ClinicalTrials.gov ID: NCT04234776
Acronym / sponsor ID: KETProject / rampty2805
Conditions: Depressive Disorder
Keywords: Ketamine, Treatment Resistant Depression
Phase: Phase 4
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 88 participants (estimated)
Lead sponsor: University of Sao PauloUniversity, hospital or other
Study start: 3 Apr 2018 (actual)
Primary completion: 3 Jun 2020 (estimated)
Study completion: 3 Apr 2021 (estimated)
First posted: 21 Jan 2020 (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: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.

Arm	Type	Receives
Rapid-acting antidepressant	Experimental	Drug: Ketamine, Diagnostic Test: Cognition, Other: Suicide risk, Other: Depression thoughts, Other: Quality of life and disability, Other: Clinical and epidemiological factors, Device: Safety of ketamine IM, Other: Tolerability of ketamine IMSubjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.
Comparator	Active comparator	Drug: Ketamine, Diagnostic Test: Cognition, Other: Suicide risk, Other: Depression thoughts, Other: Quality of life and disability, Other: Clinical and epidemiological factors, Device: Safety of ketamine IM, Other: Tolerability of ketamine IMSubjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
Moderate to severe intensity of the disease;
Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
Literate and able to understand the tasks requested;
With clinical comorbidities, however compensated;

Key exclusion criteria (13 listed)

Imminent risk of suicide;
Patients with psychoactive substance dependence;
Intellectual deficit and psychotic symptoms;
Bipolar spectrum disorders and other primary psychiatric diagnoses;
Allergic to ketamine;

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
KetamineAlso: Active comparator (escitalopram plus aripiprazole), Placebo(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole	Drug	Comparator, Rapid-acting antidepressant
CognitionComposite tools	Diagnostic test	Comparator, Rapid-acting antidepressant
Suicide riskMADRS (10) and HAM-D (3)	Other	Comparator, Rapid-acting antidepressant
Depression thoughtsEPD	Other	Comparator, Rapid-acting antidepressant
Quality of life and disabilityQuality of life and disability	Other	Comparator, Rapid-acting antidepressant
Clinical and epidemiological factorsVariables and categories	Other	Comparator, Rapid-acting antidepressant
Safety of ketamine IMVital signs	Device	Comparator, Rapid-acting antidepressant
Tolerability of ketamine IMUKU-SERS, YOUNG, CADSS and BPRS-12.	Other	Comparator, Rapid-acting antidepressant

Primary outcome

Change in depressive symptoms
Time frame: 3 times a week in once month (Phase II)
Montomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and < 50% Response: MADRS ≥ 50% Remission: MADRS ≤10
Change in depressive symptoms
Time frame: Once a week in six months (Phase III)
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)
Change in depressive symptoms
Time frame: Once a week in once month (Phase IV)
Montgomery-Åsberg Depression Rating Scale ([0-60] higher scores: worse outcome). Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).

46 secondary outcomes

Depression symptoms
Time frame: Through study completion, an average of 1 year.
Clinical impressions-S
Time frame: Through study completion, an average of 1 year.
Clinical impressions-I
Time frame: Through study completion, an average of 1 year.
Electrocardiographic monitoring
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Blood Pressure (BP [mmHg]).
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Heart rate (HR [bpm]).
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Digital pulse oximetry (%).
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Respiratory rate (RR [cycles/min])
Time frame: 3 times a week in once month (Fase II) and once a week in six months (Phase III)
Suicide risk 1
Time frame: Through study completion, an average of 1 year.
Suicide risk 2
Time frame: Through study completion, an average of 1 year.
General side effects
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Hypo/maniac symptoms
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Dissociative symptoms
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Psychotic symptoms
Time frame: 3 times a week in once month (Phase II) and once a week in six months (Phase III)
Depression thoughts
Time frame: Through study completion, an average of 1 year.
Stimate intelligence quocient
Time frame: Through study completion, an average of 1 year.
Intelligence quocient
Time frame: Through study completion, an average of 1 year.
Attention
Time frame: Through study completion, an average of 1 year.
Memory
Time frame: Through study completion, an average of 1 year.
Executive functions 1
Time frame: Through study completion, an average of 1 year.
Executive functions 2
Time frame: Through study completion, an average of 1 year.
Verbal fluency 1
Time frame: Through study completion, an average of 1 year.
Verbal fluency 2
Time frame: Through study completion, an average of 1 year.
Functional recovery 1
Time frame: Through study completion, an average of 1 year.
Functional recovery 2
Time frame: Through study completion, an average of 1 year.
Body Mass Index (BMI)
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 1
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 2
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 3
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 4
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 5
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 6
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 7
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 8
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 9
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 10
Time frame: Through study completion, an average of 1 year.
Clinical and psychiatric features 11
Time frame: Through study completion, an average of 1 year.
Epidemiological features 1
Time frame: Through study completion, an average of 1 year.
Epidemiological features 2
Time frame: Through study completion, an average of 1 year.
Epidemiological features 3
Time frame: Through study completion, an average of 1 year.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
Results publication: PubMed 17074942Rush 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.
Results publication: PubMed 25305428Bennabi D, Aouizerate B, El-Hage W, Doumy O, Moliere F, Courtet P, Nieto I, Bellivier F, Bubrovsky M, Vaiva G, Holztmann J, Bougerol T, Richieri R, Lancon C, Camus V, Saba G, Haesbaert F, d'Amato T, Charpeaud T, Llorca PM, Leboyer M, Haffen E. Risk factors for treatment resistance in unipolar depression: a systematic review. J Affect Disord. 2015 Jan 15;171:137-41. doi: 10.1016/j.jad.2014.09.020. Epub 2014 Oct 8.
Results publication: PubMed 20151847Philip NS, Carpenter LL, Tyrka AR, Price LH. Pharmacologic approaches to treatment resistant depression: a re-examination for the modern era. Expert Opin Pharmacother. 2010 Apr;11(5):709-22. doi: 10.1517/14656561003614781.
Results publication: PubMed 27486148Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2.
Results publication: PubMed 25586212Saveanu R, Etkin A, Duchemin AM, Goldstein-Piekarski A, Gyurak A, Debattista C, Schatzberg AF, Sood S, Day CV, Palmer DM, Rekshan WR, Gordon E, Rush AJ, Williams LM. The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment. J Psychiatr Res. 2015 Feb;61:1-12. doi: 10.1016/j.jpsychires.2014.12.018. Epub 2014 Dec 31.
Results publication: PubMed 23380715Perlis RH. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biol Psychiatry. 2013 Jul 1;74(1):7-14. doi: 10.1016/j.biopsych.2012.12.007. Epub 2013 Feb 4.
Results publication: PubMed 24314926McIntyre RS, Filteau MJ, Martin L, Patry S, Carvalho A, Cha DS, Barakat M, Miguelez M. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014 Mar;156:1-7. doi: 10.1016/j.jad.2013.10.043. Epub 2013 Nov 15.
Results publication: PubMed 23554581Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS Med. 2013;10(3):e1001403. doi: 10.1371/journal.pmed.1001403. Epub 2013 Mar 12.
Results publication: PubMed 25836356Millan MJ, Goodwin GM, Meyer-Lindenberg A, Ove Ogren S. Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders. Eur Neuropsychopharmacol. 2015 May;25(5):599-656. doi: 10.1016/j.euroneuro.2015.01.016. Epub 2015 Feb 7.
Results publication: PubMed 24223526Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, Vos T, Whiteford HA. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. Epub 2013 Nov 5.
Results publication: PubMed 27733282GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6.
Results publication: PubMed 30025524Machado MO, Veronese N, Sanches M, Stubbs B, Koyanagi A, Thompson T, Tzoulaki I, Solmi M, Vancampfort D, Schuch FB, Maes M, Fava GA, Ioannidis JPA, Carvalho AF. The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med. 2018 Jul 20;16(1):112. doi: 10.1186/s12916-018-1101-z.
Individual participant dataSharing planned: No

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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.

Ricardo A Moreno, MD, PhD principal investigator

Department and Institute of Psychiatry, University of Sao Paulo

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ketamine, Cognition and Suicide risk in people with Depressive Disorder, run by University of Sao Paulo at 1 site in Brazil.

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 7 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Change in depressive symptoms (time frame: 3 times a week in once month (Phase II)). The study lists 3 primary outcomes in all. 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 NCT04234776, which also lists 47 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 21 Jan 2020.