CancerPhase 1/2NCT03146806

Intranasal (NAS) Ketamine for Cancer Pain

A Phase 1/2 study testing Intranasal ketamine in people with Cancer and Pain, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cancer, Pain
What is being tested?: Intranasal ketamine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: 25 Jul 2017to 22 Apr 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 26Show fewer

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;
Placement of an intrauterine device (IUD) or intrauterine system (IUS);
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
Total abstinence or;
Male/female sterilization.
Illicit substance abuse within the past 6 months
Documented history of medication abuse/misuse (e.g. Unsanctioned dose escalation, broken opioid agreement etc.)
Clinical requirement for medications that are concurrent inducers or inhibitors of CYP3A4. CYP3A4 substrates are allowed.
Porphyria (possibility of triggering a porphyric reaction)
Severe active anemia ( a hemoglobin< 8 documented by labs drawn within 3 months of first study treatment)
History of difficult intravenous access
Intractable vomiting

Trial locations and contacts

1 site in 1 country.

United States1 site

Winship Cancer Institute
Atlanta, Georgia, 30322

Other trials in United States

About this study

Official title: Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer Related Pain

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.

Read the detailed description

There are about 11.9 million Americans affected with cancer. 53% of patients with cancer experience pain at all stages of cancer. These patients often require high doses of opioids with uncontrolled pain that makes them too sedated to effectively participate in day-to-day activities and have a good quality of life. Depression often co-exists with cancer pain due to the nature of the disease. The researchers are searching for improved therapies for chronic cancer pain and ketamine with its novel mechanism of action may be a promising solution.

Ketamine is an FDA approved anesthetic with the ability to effect memory loss, pain relief and sedation. Safety and efficacy of ketamine as an anesthetic and analgesic agent is well documented. Low doses of ketamine have minimal adverse impact on circulatory or breathing functions but can reduce pain. Research has shown that ketamine is effective in controlling breakthrough pain and reducing depression in a randomized double blind controlled trial. There is limited data regarding the use of ketamine for pain management in cancer.

One of the challenges with ketamine is the route of administration, most commonly given intravenously (IV) or intramuscularly (IM). It has also been given by mouth and rectally, but absorption is very poor. Intranasal (NAS) administration may be a promising method of delivery and can be ordered by a physician from a compounding pharmacy. From other research the investigators expect absorption to be higher than oral or rectal administration and this method of delivery as needle-free is a patient-friendly route of administration.

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 15 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the oncology clinic, 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.

Data obtained from this study will help determine if ketamine provides a reduction of pain using the Numeric Pain Rating Scale and a reduction in the use of opioid consumption and other rescue medications. Additionally the researchers will study the bioavailability, pharmacodynamics and pharmacokinetics of ketamine and the safety profile of NAS ketamine.

Conditions: Cancer, Pain
Being tested: Intranasal ketamine
Keywords: Cancer pain, Anesthesiology, Opiates, Intranasal ketamine
Medical subject headings: Neoplasms, Pain, Cancer Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intranasal ketamineDrug
Also called NAS ketamine, Ketamine hydrochloride (HCl) intranasal
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.

Study groups in NCT03146806
Study group	Role	What they receive
Intranasal ketamine treatment	Experimental	Study participants who are receiving intranasal ketamine treatments. Receives: Drug: Intranasal ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline during Visit 1 and Visit 5, up to 6 weeks

Secondary outcomes (2)

Frequency of Rescue Medication Use
The opioid sparing effect of NAS ketamine will be determined by evaluating frequency of rescue medications use prior to and during the study.
Measured: Visit 1 through Visit 5, up to 6 weeks
Total Opioid Consumption
The opioid sparing effect of NAS ketamine will be determined by evaluating total opioid consumption (rescue medication) prior to and during the study.
Measured: Visit 1 through Visit 5, up to 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jul 201722 Apr 2020

First posted10 May 2017
Study start25 Jul 2017
Primary completion22 Apr 2020
Study completion22 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CancerStudies of the same condition, open and under way.
More trials run by Emory UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03146806
Sponsor's protocol ID: IRB00086610
Status last verified: Sep 2021
First submitted: 3 May 2017
Last updated: 9 Sep 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 31038469

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer Related Pain
ClinicalTrials.gov ID: NCT03146806
Acronym / sponsor ID: IRB00086610
Conditions: Cancer, Pain
Keywords: Cancer pain, Anesthesiology, Opiates, Intranasal ketamine
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Emory UniversityUniversity, hospital or other
Study start: 25 Jul 2017 (actual)
Primary completion: 22 Apr 2020 (actual)
Study completion: 22 Apr 2020 (actual)
First posted: 10 May 2017 (actual)
Results: Posted 9 Sep 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 15 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the oncology clinic, 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.

Study design

Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intranasal ketamine treatment	Experimental	Drug: Intranasal ketamineStudy participants who are receiving intranasal ketamine treatments.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Patients with uncontrolled pain related to cancer or cancer treatment. Uncontrolled pain will be defined as:
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

Key exclusion criteria (26 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Intranasal ketamineAlso: NAS ketamine, Ketamine hydrochloride (HCl) intranasal10mg 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.	Drug	Intranasal ketamine treatment

Primary outcome

Bioavailability of Ketamine
Time frame: Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks
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.
Peak Concentration (Cmax) of Ketamine
Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks
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.
Area Under the Curve of Ketamine
Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks
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).
Time to Peak Concentration (Tmax) of Ketamine
Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks
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.
Numerical Pain Rating Scale (NPRS) Score
Time frame: Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks
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.
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score
Time frame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
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).
Montgomery Asberg Depression Rating Scale (MADRS) Score
Time frame: Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks
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.
Edmonton Symptom Assessment System (ESAS) Score
Time frame: Baseline during Study Visits 1 through 5, up to 6 weeks
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.
Eastern Cooperative Oncology Group (ECOG) Score
Time frame: Baseline during Visits 1 through 4, up to 4 weeks
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.
Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score
Time frame: Baseline during Visit 1 and Visit 5, up to 6 weeks
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.

2 secondary outcomes

Frequency of Rescue Medication Use
Time frame: Visit 1 through Visit 5, up to 6 weeks
Total Opioid Consumption
Time frame: Visit 1 through Visit 5, up to 6 weeks

Results and safety

Results posted to the registry on 9 Sep 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketamine Treatment	10	10

Primary outcome: Bioavailability of Ketamine

Time frame: Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks. Geometric mean (Standard Deviation). Unit: ng/mL

Measure	10 mg Intranasal Ketamine n = 7	10 mg Intravenous (IV) Ketamine n = 9	30 mg Intranasal Ketamine n = 10	50 mg Intranasal Ketamine n = 10
Baseline	–	0 (0)	0 (0)	0 (0)
2 minutes post-ketamine administration	13.4 (1.65)	296.4 (1.71)	23.7 (2.98)	33.7 (3.86)
30 minutes post-ketamine administration	20.3 (2.01)	35.0 (1.35)	48.6 (1.67)	51.0 (1.75)
60 minutes post-ketamine administration	11.7 (1.38)	16.4 (1.70)	26.5 (2.1)	55.8 (2.12)
240 minutes post-ketamine administration	0 (0)	0 (0)	0 (0)	0 (0)

Population analysed: The baseline measurement was not collected during the visit where 10 mg of intranasal ketamine was administered. This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Primary outcome: Peak Concentration (Cmax) of Ketamine

Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks. Geometric mean (Standard Deviation). Unit: ng/ml

Measure	10 mg Intranasal Ketamine n = 7	10 mg Intravenous (IV) Ketamine n = 9	30 mg Intranasal Ketamine n = 10	50 mg Intranasal Ketamine n = 10
Value	22.9 (1.97)	296 (1.71)	60.8 (1.90)	77.6 (2.29)

Population analysed: This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Primary outcome: Area Under the Curve of Ketamine

Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks. Geometric mean (Standard Deviation). Unit: micrograms•hour/Liter (µg•h/L)

Measure	10 mg Intranasal Ketamine n = 7	10 mg Intravenous (IV) Ketamine n = 9	30 mg Intranasal Ketamine n = 10	50 mg Intranasal Ketamine n = 10
Value	19 (NA)	113 (NA)	46 (NA)	64 (NA)

Population analysed: This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Primary outcome: Time to Peak Concentration (Tmax) of Ketamine

Time frame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks. Mean (Standard Deviation). Unit: minutes

Measure	10 mg Intranasal Ketamine n = 7	10 mg Intravenous (IV) Ketamine n = 9	30 mg Intranasal Ketamine n = 10	50 mg Intranasal Ketamine n = 10
Value	23 (3.0)	2 (1)	14 (3.8)	16 (4.4)

Population analysed: This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Data collection for adverse events began at the first study visit and were followed by a telephone call 14 days after the last dose of study medication administration, up to 6 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
10 mg Intranasal Ketamine	0 of 10 (0%)	9 of 10 (90%)	0 of 10
10 mg Intravenous (IV) Ketamine	1 of 10 (10%)	10 of 10 (100%)	0 of 10
30 mg Intranasal Ketamine	0 of 10 (0%)	9 of 10 (90%)	0 of 10
50 mg Intranasal Ketamine	2 of 10 (20%)	8 of 10 (80%)	0 of 10
Follow-up Visit	0 of 10 (0%)	5 of 10 (50%)	0 of 10
Phone Call 14 Days Post-Last Dose	0 of 10 (0%)	2 of 10 (20%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 31038469Shteamer 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vinita Singh, MD principal investigator

Emory University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intranasal ketamine in people with Cancer and Pain, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bioavailability of Ketamine (time frame: Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03146806, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.