Oral Ketamine in the Treatment of Depression and Anxiety in Patients With Cancer

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01680172
• Collaborator: (none)
• Enrollment: 5
• Locations: 2
• Arms: 2
• Duration (Months): 30
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Depression is common in patients with cancer. Current medications for depression, while effective, take several weeks to take effect. Ketamine has emerged as a drug with promise for cancer patients. In two reported cases, a single dose of ketamine induced rapid and moderately sustained symptom reduction in depression and anxiety with no adverse side effects. Benefit was seen in as little as 1 hour and sustained up to 30 days. This study is a randomized, double-blind, placebo-controlled investigation testing whether a single dose of ketamine improves depression and anxiety relative to placebo in patients with cancer.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Depression; Anxiety	Drug: Ketamine; Drug: Placebo	Phase 2

Detailed Description

Depression is common in patients with cancer. Current antidepressants, while effective, have an onset of action of at least several weeks. Ketamine has emerged as a drug with promise for cancer patients. It has been shown to potentiate opiate analgesic effects. Single dose parenteral and enteral administration studies in medically healthy treatment-resistant depressed patients have shown rapid relief of symptoms. A recent two patient case series reported a rapid and moderately sustained symptom reduction in depression and anxiety in palliative care patients following a single dose of oral ketamine 0.5 mg/kg, with no adverse effects. Benefit was seen as little as 1 hour after the administration and sustained up to 30 days. These case reports generate hypotheses of efficacy for ketamine in the treatment of depression and anxiety in patients with cancer. This study is a randomized, double-blind, placebo-controlled investigation of these hypotheses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Oral Ketamine in the Treatment of Depression and Anxiety in Patients With Cancer
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine Single dose of ketamine (0.5 mg/kg)	Drug: Ketamine; Single dose (0.5 mg/kg) of liquid ketamine 10mg/mL solution taken by mouth; Other Names: Ketalar
Placebo Comparator: Placebo Single dose of placebo	Drug: Placebo; Single dose of liquid placebo solution taken by mouth

Outcome Measures

Primary Outcome Measures

1. Hospital Anxiety and Depression Scale - Anxiety Score (HADS-A) [Baseline, 120 minutes]

   Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression.

2. Hospital Anxiety Depression Scale- Depression Score (HADS-D) [Baseline, 120 minutes]

   Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with cancer

• Outpatient status at the time of study entry

• 18 years of age or older

• Life expectancy of at least 1 month

• Regular access to a telephone (for safety reasons)

• Reliable transportation to follow-up visits

• Caregiver observation available for 24 hours after the dose

• Histologically-proven malignancy

• Depression score of >11 on the Hospital Anxiety and Depression Scale (HADS)

• Provision of informed consent

• Able to complete the patient questionnaires alone or with assistance

• Able to speak and read English

• May receive other psycho-active medications while on the study i.e. opiates, except as defined within the exclusion criteria

• May receive psychotherapy from an outside provider at the beginning and/or during the course of the study

Exclusion Criteria:

• Obvious cognitive dysfunction or Mini Mental Status Exam score <20

• Antidepressants started or dose changed within 8 weeks of the beginning of the study or during the study

• Benzodiazepines prescribed for psychiatric indications that have been started or dose change within 2 weeks of the beginning of study enrollment

• Suicidal ideation or a suicide attempt within the last year

• Patients with current or past psychosis not from delirium

• Females who are pregnant or nursing

• Unable to take oral medications

• Primary or metastatic brain malignancy

• Gastrointestinal tract obstruction

• Prior adverse reaction to or other contraindication to ketamine

• Substance abuse or dependence, as defined by Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, within the last 90 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Yuma Regional Medical Center	Yuma	Arizona	United States	85364

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Robert P. Bright, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert P. Bright, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01680172
• Other Study ID Numbers: 12-001156
• First Posted: Sep 7, 2012
• Last Update Posted: Feb 29, 2016
• Last Verified: Jan 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Robert P. Bright, Principal Investigator, Mayo Clinic: cancer; depression; anxiety; palliative care
• Additional relevant MeSH terms: Depression; Depressive Disorder; Anxiety Disorders; Ketamine

Study Results

Participant Flow

Recruitment Details	Participants were recruited at Mayo Clinic in Scottsdale, Arizona from 2012 to 2014.

Arm/Group Title	Ketamine	Placebo
Arm/Group Description	Single dose of ketamine (0.5 mg/kg) Ketamine: Single dose of ketamine (0.5 mg/kg)	Single dose of placebo Placebo: Single dose of placebo
Period Title: Overall Study
STARTED	3	2
COMPLETED	3	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ketamine	Placebo	Total
Arm/Group Description	Single dose of ketamine (0.5 mg/kg) Ketamine: Single dose of ketamine (0.5 mg/kg)	Single dose of placebo Placebo: Single dose of placebo	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	0 0%	3 60%
>=65 years	0 0%	2 100%	2 40%
Sex: Female, Male (Count of Participants)
Female	2 66.7%	1 50%	3 60%
Male	1 33.3%	1 50%	2 40%
Region of Enrollment (participants) [Number]
United States	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Hospital Anxiety and Depression Scale - Anxiety Score (HADS-A)
Description	Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression.
Time Frame	Baseline, 120 minutes

Outcome Measure Data

Analysis Population Description

Study was terminated early due to slow accrual.

Arm/Group Title	Ketamine	Placebo
Arm/Group Description	Single dose of ketamine (0.5 mg/kg) Ketamine: Single dose of ketamine (0.5 mg/kg)	Single dose of placebo Placebo: Single dose of placebo
Measure Participants	3	2
HADS-A score at baseline	12.3 (2.5)	16.5 (4.9)
HADS-A Score at 120 minutes post dose	7.7 (3.8)	11.0 (5.7)

2. Primary Outcome

Title	Hospital Anxiety Depression Scale- Depression Score (HADS-D)
Description	Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression.
Time Frame	Baseline, 120 minutes

Outcome Measure Data

Analysis Population Description

Study was terminated early due to slow accrual.

Arm/Group Title	Ketamine	Placebo
Arm/Group Description	Single dose of ketamine (0.5 mg/kg) Ketamine: Single dose of ketamine (0.5 mg/kg)	Single dose of placebo Placebo: Single dose of placebo
Measure Participants	3	2
HADS-D Score at baseline	12.7 (1.5)	14.5 (2.1)
HADS-D Score 120 minutes post dose	11.7 (2.3)	10.5 (3.5)

Adverse Events

Time Frame	Adverse events were evaluated at baseline, 60 minutes and 120 minutes after study drug administration and Days 2, 7, 14 and 28 after study drug administration.
Arm/Group Title	Ketamine		Placebo
Arm/Group Description	Single dose of ketamine (0.5 mg/kg) Ketamine: Single dose of ketamine (0.5 mg/kg)		Single dose of placebo Placebo: Single dose of placebo
All Cause Mortality
	Ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		2/2 (100%)
Cardiac disorders
Rapid Heart Rate	1/3 (33.3%)	1	1/2 (50%)	1
Chest Pain	1/3 (33.3%)	1	0/2 (0%)	0
Gastrointestinal disorders
Vomiting	0/3 (0%)	0	1/2 (50%)	1
General disorders
Headache	2/3 (66.7%)	2	1/2 (50%)	1
Impaired Concentration	0/3 (0%)	0	2/2 (100%)	2
Drowsiness	2/3 (66.7%)	2	2/2 (100%)	2
Dizziness	1/3 (33.3%)	1	1/2 (50%)	1
Lightheaded	1/3 (33.3%)	1	1/2 (50%)	1
Confusion	1/3 (33.3%)	1	1/2 (50%)	1
Disorientation	1/3 (33.3%)	1	1/2 (50%)	1
Feeling high	1/3 (33.3%)	1	0/2 (0%)	0
Feeling of floating	1/3 (33.3%)	1	0/2 (0%)	0
Nervous system disorders
Tingling sensation on skin	1/3 (33.3%)	1	1/2 (50%)	1
Psychiatric disorders
Impaired judgement	1/3 (33.3%)	1	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath	2/3 (66.7%)	2	2/2 (100%)	2

Limitations/Caveats

The study was terminated due to slow accrual rate. Data analysis limited to 5 participants.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.