Intranasal (NAS) Ketamine for Cancer Pain

NCT03146806 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB00086610
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to determine the safety, feasibility, and utility of intranasal (NAS) ketamine in persistent uncontrolled cancer related pain. In this prospective clinical trial the researchers will investigate the use of NAS ketamine in patients with pain related to cancer or cancer treatment. The researchers plan to enroll at least 25 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the supportive oncology clinic, oncology clinics, the pain clinic and Acute Pain Service at Emory. Participants will be asked to return to the Phase I unit of the Winship Cancer Building C for a total of 5 study visits, each two to five days apart. During these visits participants will complete questionnaires, have blood samples drawn and will have study medication administered to them in escalating doses. For safety monitoring participants will be contacted by telephone 14 days after the last dose of medication administered.

Conditions

Cancer; Pain

Keywords

Cancer pain; Anesthesiology; Opiates; Intranasal ketamine

Outcome Measures

Primary Outcomes (19)

• Bioavailability of Ketamine

  Blood samples were obtained at the study visits where ketamine was administered to measure the bioavailability (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Bioavailability is assessed as nanograms per milliliter (ng/mL) of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained prior to ketamine administration, and at 2, 30, 60 and 240 minutes after medication administration, during study visits 1 through 4. The baseline sample was not collected at the first study visit as assessing prior intake of ketamine was not necessary.

  Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks

• Peak Concentration (Cmax) of Ketamine

  Blood samples were obtained at the study visits where ketamine was administered to measure the peak concentration (Cmax) of intranasal and intravenous ketamine. Peak concentration is assessed as the maximum ng/mL of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration.

  Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks

• Area Under the Curve of Ketamine

  Blood samples were obtained at the study visits where ketamine was administered to measure the elimination (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Elimination of the drug disappearing from the body is assessed as the area under the curve (AUC). Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration. Each subject did not have quantitative levels at all time points. There were not enough data to construct a curve for each participant and therefore calculate an AUC. Data from all participants were naively pooled to calculate one AUC for the entire population (i.e., across all participants' data).

  Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks

• Time to Peak Concentration (Tmax) of Ketamine

  Blood samples were obtained at the study visits where ketamine was administered to measure the time to peak concentration (Tmax) of intranasal and intravenous ketamine. Time is measured as minutes after administration when the maximum concentration of ketamine in blood is reached.

  Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks

• Numerical Pain Rating Scale (NPRS) Score

  The Numerical Pain Rating Scale (NPRS) was used to evaluate patient reported pain. Pain scores were recorded prior to and at 5,10,15, 30, 45, 60, 120, 180 and 240 minutes after administration of ketamine. The NPRS asks participants rate their current level of pain intensity on a scale from 0 (no pain) to 10 (worst possible pain). In general, improvements of pain severity of 1.5 points or less on NPRS could be seen as clinically irrelevant. Above that value, the cutoff point for "clinical relevance" depends on patients' baseline pain severity, and ranges from 2.4 to 5.3. Higher baseline scores require larger raw changes to represent clinically important differences.

  Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score

  To evaluate self-reported fatigue, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score

  To evaluate self-reported dizziness, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score

  To evaluate self-reported nausea, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score

  To evaluate self-reported headache, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score

  To evaluate self-reported feeling of unreality, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score

  To evaluate self-reported change in hearing, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score

  To evaluate self-reported change in vision, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score

  To evaluate self-reported mood change, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score

  To evaluate self-reported general discomfort, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score

  To evaluate self-reported hallucinations, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome).

  Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

• Montgomery Asberg Depression Rating Scale (MADRS) Score

  Depression was assessed on the Montgomery Asberg Depression Rating Scale (MADRS) during each study visit, before medication administration and 180 minutes after medication administration. The MADRS is designed to be particularly sensitive to treatment effects. The MADRS is a 10-item scale where the survey administrator rates the participant on a variety of aspects related to depression (such as apparent sadness, tension, and pessimistic thoughts) based on a clinical interview. Responses are provided on a scale of 0 to 6 where 0 signifies no difficulties in this area and 6 signifies severe difficulty. Total scores range from 0 to 60 with higher scores indicating greater severity of depression.

  Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks

• Edmonton Symptom Assessment System (ESAS) Score

  The Edmonton Symptom Assessment System (ESAS) assesses nine symptoms that are common in cancer patients: pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and well-being. Each symptom is rated on a scale ranging from 0 (absence of symptom) to 10 (worst possible degree of symptom). The ESAS was administered at the baseline time point at each study visit.

  Baseline during Study Visits 1 through 5, up to 6 weeks

• Eastern Cooperative Oncology Group (ECOG) Score

  The Eastern Cooperative Oncology Group (ECOG) score evaluates performance status of the participants by rating their ability to perform physical tasks and self care. Responses are 0 (fully active), 1 (restricted in physical strenuous activity but ambulatory), 2 (ambulatory and capable of all self-care but unable to carry out work activities), 3 (capable of only limited self-care), 4 (completely disabled), or 5 (dead). The ECOG score will be obtained at the baseline time point at each study visit where medication is administered.

  Baseline during Visits 1 through 4, up to 4 weeks

• Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score

  The PROMIS Global Health questionnaire, version 1.1, consists of 10 items assessing general domains of health and functioning. Items are scored on a 5-point scale where 1 = poor and 5 = excellent. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10. Scores above 50 indicate better health and functioning, while scores below 50 indicate physical, mental and social health that is below average.

  Baseline during Visit 1 and Visit 5, up to 6 weeks

Secondary Outcomes (2)

• Frequency of Rescue Medication Use

  Visit 1 through Visit 5, up to 6 weeks

• Total Opioid Consumption

  Visit 1 through Visit 5, up to 6 weeks

Study Arms (1)

Intranasal ketamine treatment

EXPERIMENTAL

Study participants who are receiving intranasal ketamine treatments.

Drug: Intranasal ketamine

Interventions

Intranasal ketamine DRUG

10mg of intranasal ketamine will be given to make sure that the study patients are able to tolerate a small dose of NAS ketamine. On the second visit, 10 mg of IV ketamine will be given to help establish bioavailability of NAS ketamine, with patients serving as their own controls. On the third and fourth visit, higher doses of ketamine, 30 mg and 50 mg respectively, will be given. All doses of ketamine will be administered by an anesthesia research nurse.

Also known as: NAS ketamine, Ketamine hydrochloride (HCl) intranasal

Intranasal ketamine treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with uncontrolled pain related to cancer or cancer treatment. Uncontrolled pain will be defined as:
• Pain which persists for more than 7 days and is rated \>/=4 on Numerical Pain Rating Score (NPRS)
• Use of breakthrough medication more than 4 times in 24 hours or being treated with oral morphine equivalent of 50 mg/d or more
• Patients who are able to follow-up in person during the trial
• Patient on stable analgesic regimen for \>7 days without escalation during study period with rescue or immediate release medication every 3 hours or longer
• Patients who are willing and able to maintain a daily pain diary
• Patients who are able to understand written and verbal English
• Patient weight \>/= 50 kg

You may not qualify if:

• Transportation issues interfering with return study visits
• Patients with high disposition of laryngospasm or apnea
• Presence of severe cardiac disease
• Presence of conditions where significant elevations in blood pressure would be a serious hazard.
• Stage 2 hypertension or greater (systolic blood pressure \> 160 and/or diastolic blood pressure \>100)
• Baseline tachycardia, heart rate (HR) \>100
• History of seizures, elevated intracranial pressure (ICP) or cerebrospinal fluid (CSF) obstructive states (e.g. severe head injury, central congenital or mass lesions)
• Conditions that may increase intraocular pressure (e.g. glaucoma, acute globe injury)
• History of uncontrolled depression or other psychiatric comorbidity with psychosis
• History of liver disease
• History of interstitial cystitis
• History of nasal or sinus anomalies or dysfunction e.g. allergic or infectious rhinitis.
• Patients with lesions to the nasal mucosa
• Pregnant women, nursing mothers and women of childbearing potential not using contraception known to be highly effective. Highly effective contraception methods include combination of any two of the following:
• Use of oral, injected or implanted hormonal methods of contraception or;

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Shteamer JW, Harvey RD, Spektor B, Curseen K, Egan K, Chen Z, Gillespie TW, Sniecinski RM, Singh V. Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial. JMIR Res Protoc. 2019 Apr 30;8(4):e12125. doi: 10.2196/12125.

  PMID: 31038469 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Pain; Cancer Pain

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Vinita Singh, MD
• Organization: Emory University

vinita.singh@emory.edu

404-686-2410

Study Officials

• Vinita Singh, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 10, 2017
• Study Start: July 25, 2017
• Primary Completion: April 22, 2020
• Study Completion: April 22, 2020
• Last Updated: September 9, 2021
• Results First Posted: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)