Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001130358
Ethics application status
Approved
Date submitted
27/07/2017
Date registered
2/08/2017
Date last updated
17/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of Ketamine in Elderly Patients with Depression.
Scientific title
Pilot study evaluating the efficacy of subcutaneous ketamine for the treatment of depression in the elderly.
Secondary ID [1] 292544 0
Nil known
Universal Trial Number (UTN)
Trial acronym
KED (Ketamine Elderly Depression)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 304199 0
Condition category
Condition code
Mental Health 303535 303535 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Phase 1: Open label subcutaneous (SC) ketamine (single doses of 0.3 and 0.6 mg/kg, in that order) in patients with major depressive disorder (MDD) (n=24). All patients will receive both the 0.3mg/kg and the 0.6mg/kg dose in that order, duration between the two doses will be one week. Phase 2: Patients completing Phase 1 and who had at least 50% reduction in depression ratings - reduction in score on the Geriatric Depression Scale (GDS) - in response to any dose of ketamine are eligible to receive 1-2x weekly ketamine dosing for up to 3 months to help maintain improvement in depression symptoms. Subcutaneous doses administered at individualised dose, frequency (1-2 times per week) and duration (up to 3 months) will be at the discretion of the treating physician based on phase 1 response.
Intervention code [1] 298741 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302905 0
Change in depression rating scale (GDS: Geriatric Depression Scale.
Timepoint [1] 302905 0
Change in depression rating scale (GDS: Geriatric Depression Scale – predose, 1h, 2h, 24h, 72h and 168h. Primary endpoint is change at 24h. This is applicable to both doses administered at phase 1.
Secondary outcome [1] 337398 0
Phase 2: GDS score.
Timepoint [1] 337398 0
Phase 2: GDS score predose and 2 hours post dose. This will be repeated at every phase 2 dose administered.

Eligibility
Key inclusion criteria
To be included in the study, participants must meet all of the following inclusion criteria:
1. Capable of understanding and signing an informed consent
2. Aged > 65 years on the day of consent.
3. Psychiatric history: Participants will be assessed using DSM-5 criteria (APA, 2013) via a standardized clinical psychiatric interview conducted by a trained examiner.
4. Patients with MDD: Baseline GDS > 9.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
To be included in the study, participants must meet none of the following exclusion criteria:
1. Participants who, in the opinion of the investigator, do not understand the information and procedures of the study, or would not be compliant with them (in particular the study restrictions and risks involved).
2. Any participant for whom the investigator believes, for any reason, that participation would not be an acceptable risk.
3. Patients with severe unstable acute or chronic medical illnesses.
4. Patients with current active suicidal ideation.
5. Any history of an additional axis I diagnosis (not including adjustment disorder, simple phobia, dysthymia or comorbid anxiety) is exclusionary.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This is a two phase open-label study.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Demographic and Background Characteristics: Summary statistics will be calculated and reported for demographic, vital signs, and rating scale data. Categorical variables will be reported using counts and percentages. In order to accommodate the repeated measures on patients, from both the multiple measurements over time within a given dose, and from the two doses received by each participant in Phase 1 (the ascending dose design), linear mixed models will be used with random participant and participant-dose effects, along with fixed effects for time, dose, and the time-by-dose interaction for Phase 1 data. Residual maximum likelihood estimates will be used. Histograms and scatter plots of conditional residuals will be inspected and, where appropriate, natural logarithm transformations investigated to see if this improves satisfaction of model assumptions. As this is an exploratory study, and to avoid reducing power to detect both beneficial and adverse effects, no adjustments for multiple comparisons will be made. A responder analysis will be performed based on the proportion of participants with 50% or greater reduction in GDS total score after either dose in Phase 1.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
24/09/2018
Actual
Date of last participant enrolment
Anticipated
31/12/2019
Actual
Date of last data collection
Anticipated
30/04/2020
Actual
Sample size
Target
24
Accrual to date
0
Final
Recruitment outside Australia
Country [1] 9097 0
New Zealand
State/province [1] 9097 0
Otago

Funding & Sponsors
Funding source category [1] 297116 0
University
Name [1] 297116 0
University of Otago
Country [1] 297116 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
P.O. Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 296129 0
None
Name [1] 296129 0
Address [1] 296129 0
Country [1] 296129 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298294 0
Sothern Health and Disability Committee
Ethics committee address [1] 298294 0
Ministry of Health
P.O. Box 5013
Wellington 6011
Ethics committee country [1] 298294 0
New Zealand
Date submitted for ethics approval [1] 298294 0
21/08/2017
Approval date [1] 298294 0
30/01/2018
Ethics approval number [1] 298294 0

Summary
Brief summary
Major depressive disorder in the elderly (MDDE) can often present as a severe form of MDD associated with suicide, longer inpatient stay and overall worse prognosis than other forms of MDD. Furthermore, In a US study of hospitalized participants with MDD, 25% met the criteria for MDD with psychotic features and this was even more prevalent amongst the elderly (Coryell et al., 1984).
Elderly MDDE patients present a unique treatment challenge to clinicians, since they often exhibit needs quite different from those of MDD patients due to substantial physical comorbidity and variations in response to therapy. MDDE is probably heterogeneous and its aetiopathogenesis is complex. Treatment of MDDE is currently only loosely based on guidelines. Unfortunately, there is a considerable dearth of literature involving evidence-based clinical practice guidelines and randomized controlled trials in individuals with MDDE. Treatment guidelines for MDDE are lacking and the evidence is limited regarding the most effective pharmacological treatment. Furthermore, there are only a small number of treatment studies in elderly patients with psychotic depression. The rates of MDDE with psychotic features are higher in the elderly and they respond poorly to treatment with medication (Kok et al., 2010; Croucher et al., 2017).

This year two reports emphasized the need to study the role of Ketamine in MDDE. Ketamine is a dissociative anaesthetic, which provides antagonism on the N-methyl-D-aspartate (NMDA) receptor. Several studies have demonstrated rapid anti-depressant and anti-suicidal effects from the administration of ketamine in adult patients (Katalinic, 2013) but studies in MDDE are few. A case report on a patient in late life who suffered from treatment-resistant MDDE and was treated with ketamine achieving remission has been published recently (Heard et al., 2017). An additional encouraging report focused on MDDE patients treated by ECT. Although ECT has been shown to be efficacious in depressed older adults, a subgroup of patients may show either limited or no response to this intervention. Ketamine, has been shown to rapidly improve depressive symptoms and suicidal ideation when given in addition to ECT in the elderly (Saxena & Espinoza, 2017). There are also positive recently published safety and efficacy data in 16 elderly geriatric depressed patients from a group in Sydney, Australia, with ketamine doses ranging from 0.1 to 0.5 mg/kg (George et al., 2017).
Study Objectives:
1. To evaluate the effect of ketamine on depression ratings in elderly patients with MDD.
2. To evaluate the safety and tolerability of ketamine in elderly patients with MDD
3. To evaluate the potential for repeat-dose ketamine to sustain reductions in depression in elderly patients with MDD
Trial website
None
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76618 0
A/Prof Yoram Barak
Address 76618 0
Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054
Country 76618 0
New Zealand
Phone 76618 0
+64-3-4740999 ext 8113
Fax 76618 0
Email 76618 0
[email protected]
Contact person for public queries
Name 76619 0
A/Prof Yoram Barak
Address 76619 0
Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054
Country 76619 0
New Zealand
Phone 76619 0
+64-3-4740999 ext 8113
Fax 76619 0
Email 76619 0
[email protected]
Contact person for scientific queries
Name 76620 0
Prof Paul Glue
Address 76620 0
Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054
Country 76620 0
New Zealand
Phone 76620 0
+64-21-2433372
Fax 76620 0
Email 76620 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23544Study protocol    373390-(Uploaded-07-10-2020-14-30-36)-Study-related document.docx
23545Informed consent form    373390-(Uploaded-07-10-2020-14-31-50)-Study-related document.doc
23546Statistical analysis plan    See the study protocol.
23547Clinical study report    Will be uploaded after trial completion
23548Ethical approval    Approval will be uploaded.

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.