ANZCTR - Registration

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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

15/12/2024

Date data sharing statement initially provided

15/12/2024

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]

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

Condition category

Condition code

Mental Health

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Change in depression rating scale (GDS: Geriatric Depression Scale.

Timepoint [1]

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]

Phase 2: GDS score.

Timepoint [1]

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?

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)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

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

Withdrawn

Reason for early stopping/withdrawal

Participant recruitment difficulties

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Otago

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Otago

Address [1]

P.O. Box 56
Dunedin 9054

Country [1]

New Zealand

Primary sponsor type

University

Name

University of Otago

Address

P.O. Box 56
Dunedin 9054

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sothern Health and Disability Committee

Ethics committee address [1]

Ministry of Health
P.O. Box 5013
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

21/08/2017

Approval date [1]

30/01/2018

Ethics approval number [1]

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

A/Prof Yoram Barak

Address

Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054

Country

New Zealand

Phone

+64-3-4740999 ext 8113

Fax

Yoram.Barak@otago.ac.nz

Contact person for public queries

Name

Yoram Barak

Address

Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054

Country

New Zealand

Phone

+64-3-4740999 ext 8113

Fax

Yoram.Barak@otago.ac.nz

Contact person for scientific queries

Name

Paul Glue

Address

Otago University
Dunedin School of Medicine.
Dept Psychological Medicine.
P.O. Box 56
Dunedin 9054

Country

New Zealand

Phone

+64-21-2433372

Fax

Paul.Glue@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

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.

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