Trial Outcomes & Findings for Treatment Resistant Depression (Pilot) (NCT NCT01179009)

Last Updated: 2023-09-15

Results Overview

The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale that measures the severity of depression, with a higher score indicating a higher level of depression. The range of scores is 0 to 60.

Recruitment status

COMPLETED

Study phase

Target enrollment

20 participants

Primary outcome timeframe

8 weeks

Results posted on

2023-09-15

Participant Flow

From 2012-2014, participants were recruited via referrals and clinicaltrials.gov at Washington University School of Medicine in St. Louis, Missouri.

Participant milestones

Participant milestones
Measure	Ketamine 100-hour Infusion 100-hour infusion of ketamine plus a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. Scopolamine Transdermal Product: Some participants will receive a scopolamine transdermal patch prior to and throughout their infusion/injections visits.	Ketamine 40-minute Infusion 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. placebo: IV saline (i.e. placebo ketamine)
Overall Study STARTED	10	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment Resistant Depression (Pilot)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ketamine 100-hour Infusion n=10 Participants 100-hour infusion of ketamine plus a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. Scopolamine Transdermal Product: Some participants will receive a scopolamine transdermal patch prior to and throughout their infusion/injections visits.	Ketamine 40-minute Infusion n=10 Participants 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. placebo: IV saline (i.e. placebo ketamine)	Total n=20 Participants Total of all reporting groups
Age, Continuous	42.5 years STANDARD_DEVIATION 13.8 • n=93 Participants	46.6 years STANDARD_DEVIATION 12.8 • n=4 Participants	44.6 years STANDARD_DEVIATION 13.1 • n=27 Participants
Sex: Female, Male Female	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	2 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	9 Participants n=93 Participants	10 Participants n=4 Participants	19 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Family History of Alcoholism Yes	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants
Family History of Alcoholism No	3 Participants n=93 Participants	6 Participants n=4 Participants	9 Participants n=27 Participants
Family History of Alcoholism Unknown	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
CGI - Severity of Illness 1 = Normal	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
CGI - Severity of Illness 2 = Borderline mentally ill	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
CGI - Severity of Illness 3 = Mildly ill	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
CGI - Severity of Illness 4 = Moderately ill	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
CGI - Severity of Illness 5 = Markedly ill	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants
CGI - Severity of Illness 6 = Severely ill	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
CGI - Severity of Illness 7 = Among the most extremely ill patients	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Lifetime Major Depressive Episodes Single	3 Participants n=93 Participants	5 Participants n=4 Participants	8 Participants n=27 Participants
Lifetime Major Depressive Episodes Recurrent	7 Participants n=93 Participants	5 Participants n=4 Participants	12 Participants n=27 Participants
Age of First Major Depressive Episode	18.2 years STANDARD_DEVIATION 6.1 • n=93 Participants	22.0 years STANDARD_DEVIATION 5.4 • n=4 Participants	20.1 years STANDARD_DEVIATION 6.0 • n=27 Participants
Duration of Current Episode	8.7 years STANDARD_DEVIATION 8.6 • n=93 Participants	16.6 years STANDARD_DEVIATION 12.8 • n=4 Participants	12.7 years STANDARD_DEVIATION 11.4 • n=27 Participants
Number of Antidepressant Trials	18.4 trials n=93 Participants	16.8 trials n=4 Participants	17.6 trials n=27 Participants
Total MADRS Score	31.9 units on a scale STANDARD_DEVIATION 5.9 • n=93 Participants	34.0 units on a scale STANDARD_DEVIATION 3.8 • n=4 Participants	33.0 units on a scale STANDARD_DEVIATION 4.9 • n=27 Participants
Baseline HAM-D Score	22.1 units on a scale STANDARD_DEVIATION 5.3 • n=93 Participants	21.6 units on a scale STANDARD_DEVIATION 2.8 • n=4 Participants	21.9 units on a scale STANDARD_DEVIATION 4.1 • n=27 Participants

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Outcome measures
Measure	Ketamine 100-hour Infusion n=10 Participants 100-hour infusion of ketamine plus a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. Scopolamine Transdermal Product: Some participants will receive a scopolamine transdermal patch prior to and throughout their infusion/injections visits.	Ketamine 40-minute Infusion n=10 Participants 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. placebo: IV saline (i.e. placebo ketamine)
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-9.0 Scores on a scale Standard Deviation 9.5	-6.4 Scores on a scale Standard Deviation 8.7

PRIMARY outcome

Timeframe: 8 weeks

The Clinical Global Improvement is a 7-point scale where the anchors range from 1 (very much improved) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Ketamine 100-hour Infusion n=10 Participants 100-hour infusion of ketamine plus a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. Scopolamine Transdermal Product: Some participants will receive a scopolamine transdermal patch prior to and throughout their infusion/injections visits.	Ketamine 40-minute Infusion n=10 Participants 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. placebo: IV saline (i.e. placebo ketamine)
Clinical Global Impression (CGI) Global Improvement Score. Minimally improved	1 Participants	0 Participants
Clinical Global Impression (CGI) Global Improvement Score. No change	5 Participants	5 Participants
Clinical Global Impression (CGI) Global Improvement Score. Minimally worse	0 Participants	3 Participants
Clinical Global Impression (CGI) Global Improvement Score. Much worse	0 Participants	0 Participants
Clinical Global Impression (CGI) Global Improvement Score. Very much improved	2 Participants	1 Participants
Clinical Global Impression (CGI) Global Improvement Score. Much improved	2 Participants	1 Participants
Clinical Global Impression (CGI) Global Improvement Score. Very much worse	0 Participants	0 Participants

Adverse Events

Ketamine 100-hour Infusion

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Ketamine 40-minute Infusion

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Michael Yingling

Washington University

Phone: 5735791412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Ketamine 100-hour Infusion n=10 participants at risk 100-hour infusion of ketamine plus a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. Scopolamine Transdermal Product: Some participants will receive a scopolamine transdermal patch prior to and throughout their infusion/injections visits.	Ketamine 40-minute Infusion n=10 participants at risk 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine) Ketamine: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). Clonidine: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. placebo: IV saline (i.e. placebo ketamine)
General disorders Visual distortions and hallucinations	70.0% 7/10 • Number of events 7 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	40.0% 4/10 • Number of events 4 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Unusual thoughts and delusions	70.0% 7/10 • Number of events 7 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	50.0% 5/10 • Number of events 5 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Incoherent	20.0% 2/10 • Number of events 2 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	10.0% 1/10 • Number of events 1 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Disorientation	30.0% 3/10 • Number of events 3 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	20.0% 2/10 • Number of events 2 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Decreased Concentration/Memory Loss	100.0% 10/10 • Number of events 10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	100.0% 10/10 • Number of events 10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Restlessness	100.0% 10/10 • Number of events 10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	80.0% 8/10 • Number of events 8 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Anxiety	100.0% 10/10 • Number of events 10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	100.0% 10/10 • Number of events 10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Palpitations	30.0% 3/10 • Number of events 3 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	40.0% 4/10 • Number of events 4 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Insomnia	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	80.0% 8/10 • Number of events 8 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Involuntary Movements	10.0% 1/10 • Number of events 1 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	30.0% 3/10 • Number of events 3 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Headache	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	80.0% 8/10 • Number of events 8 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Dizziness	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Nausea	60.0% 6/10 • Number of events 6 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	70.0% 7/10 • Number of events 7 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Vomiting	10.0% 1/10 • Number of events 1 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	10.0% 1/10 • Number of events 1 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Diplopia	30.0% 3/10 • Number of events 3 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	40.0% 4/10 • Number of events 4 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Sedation	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Nystagmus	90.0% 9/10 • Number of events 9 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	60.0% 6/10 • Number of events 6 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Hypersalivation	0.00% 0/10 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	20.0% 2/10 • Number of events 2 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.
General disorders Erythema/Rash	50.0% 5/10 • Number of events 5 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.	40.0% 4/10 • Number of events 4 • Symptoms were measured 4 times daily over the course of the 4-day infusion using the Brief Psychiatric Rating Scale and the Clinical and Adverse Events Checklist. For symptoms that occurred on more than one assessment, the highest severity rating is reported.