Feasibility Study of Oral Ketamine Versus Placebo for the Treatment of Anxiety in Patients With Pancreatic Cancer

Cedars-Sinai Medical Center

Status and phase: Enrolling; Early Phase 1

Conditions: Anxiety; Pancreatic Cancer

Treatments: Drug: Placebo; Drug: Ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05086250

IIT2019-18-IRWIN-KETANX

Details and patient eligibility

About

This is a prospective, single center, double blind, randomized, crossover feasibility study of oral ketamine versus placebo for the treatment of anxiety in patients with pancreatic cancer currently receiving or within 12 weeks of receiving cancer targeted therapy. The primary objective is to determine the feasibility of enrolling subjects and treatment adherence. The secondary objectives are to describe the safety and tolerability. Exploratory objectives are to assess the effect of ketamine/placebo on Depression, Anxiety, Physical Function, Pain Interference, Pain Intensity, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities as measured by PROMIS Anxiety Short Form 7a and the PROMIS-29 Profile v2.1 of Patient Reported Outcomes, as well as changes in circulatory inflammatory cytokines, blood glutamine levels, and other biomarkers of anxiety and/or depression.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Ability to understand and the willingness to sign a written informed consent.
2. Participant has been diagnosed with pancreatic cancer.
3. Receiving or within twelve weeks of having received cancer targeted treatment, including surgery, radiation, chemotherapy, immunotherapy, or other cancer targeted therapy.
4. Age ≥ 18 years.
5. Has moderate to severe anxiety according to the PROMIS Anxiety Short Form 7a and/or PROMIS-29 anxiety module (T-score of > 60).
6. Documented adequate liver function within the screening period.
7. Use of concomitant standard antidepressants targeting anxiety (e.g. SSRIs) is permitted if dose has been the same for at least 12 weeks prior to study entry and patient still meets inclusion #5.
8. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and while receiving study drug. Women of child-bearing potential must have a negative urine or blood pregnancy test at screening. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and study staff immediately.
9. Must be able to read and understand English.
10. Required not to engage in potentially hazardous activities, such as driving a motor vehicle or operating machinery, after receiving a medication dose until the next day after a restful sleep (as per recommendations with Spravato).
11. Agrees to abstain from alcohol use while taking study medication.

Exclusion criteria

1. Initial cancer diagnosis ≤6 weeks prior to Day 0.
2. Meets MINI International Neuropsychiatric Interview (MINI Plus), criteria for diagnoses of schizophrenia, bipolar illness, delirium or psychosis.
3. Scores ≥ 10 on the Suicidal Risk Assessment (SRA).
4. History of allergic reactions or hypersensitivity to ketamine.
5. Documented history of severe cardiac insufficiency (NYHA III or IV), with currently uncontrolled and/or unstable cardiac or coronary artery disease.
6. Current or recent significant tachyarrhythmia, severe angina, or myocardial ischemia, as assessed by a study physician.
7. Documented history of poorly controlled hypertension (Systolic Blood Pressure > 180 mmHG or Diastolic Blood Pressure > 100 mmHG twice within a one-month period in last two months), with or without antihypertensives.
8. Women who are pregnant or nursing or expect to become pregnant or start nursing during the expected trial duration, and women of childbearing potential who refuse to use contraceptives to prevent childbearing.
9. Uncontrolled hypo- or hyperthyroidism, as assessed by a study physician.
10. Diagnosis of dementia.
11. Treatment with monoamine oxidase inhibitor (MAOI) within 14 days of Day 0.
12. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
13. History of intracerebral hemorrhage.
14. Refusal/inability to comply with inclusion criterion #10 (driving restrictions) and inclusion criterion #11 (alcohol abstinence) during study treatment period.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 2 patient groups

Arm A: Ketamine Followed by Placebo

Experimental group

Description:

Weekly oral administration of 0.5mg/kg ketamine for 4 weeks, followed by weekly oral administration of placebo for 4 weeks (separated by a washout period of 2 weeks).

Treatment:

Drug: Ketamine

Drug: Ketamine

Drug: Placebo

Drug: Placebo

Arm B: Placebo Followed by Ketamine

Experimental group

Description:

Weekly oral administration of placebo for 4 weeks, followed by weekly oral administration of 0.5mg/kg ketamine for 4 weeks (separated by a washout period of 2 weeks).

Treatment:

Drug: Ketamine

Drug: Ketamine

Drug: Placebo

Drug: Placebo