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

Depressive Disorder Clinical Trial

— KETProject  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04234776
• Other study ID #: rampty2805
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: April 3, 2018
• Est. completion date: April 3, 2021

Study information

• Verified date: December 2019
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 88
• Est. completion date: April 3, 2021
• Est. primary completion date: June 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);

2. Moderate to severe intensity of the disease;

3. Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);

a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,

4. Literate and able to understand the tasks requested;

5. With clinical comorbidities, however compensated;

6. Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.

Exclusion Criteria:

1. Imminent risk of suicide;

2. Patients with psychoactive substance dependence;

3. Intellectual deficit and psychotic symptoms;

4. Bipolar spectrum disorders and other primary psychiatric diagnoses;

5. Allergic to ketamine;

6. Glaucoma;

7. Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;

8. Treatment with irreversible MAOI in two weeks prior to visit 0;

9. Fluoxetine treatment within 4 weeks prior to visit 0;

10. Treatment with others antidepressants;

11. Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;

a. Lorazepam and zolpidem may be used;

12. Patients who become pregnant will be excluded from the study and referred for obstetric care.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• Ketamine
(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole

Diagnostic Test:
• Cognition
Composite tools

Other:
• Suicide risk
MADRS (10) and HAM-D (3)
• Depression thoughts
EPD
• Quality of life and disability
Quality of life and disability
• Clinical and epidemiological factors
Variables and categories

Device:
• Safety of ketamine IM
Vital signs

Other:
• Tolerability of ketamine IM
UKU-SERS, YOUNG, CADSS and BPRS-12.

Locations

Country	Name	City	State
Brazil	Núcleo de Pesquisas em Saúde Mental	Blumenau	Santa Catarina

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (46)

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* Note: There are 46 references in all — Click here to view all references

Outcome

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