The purpose of this study is to evaluate the efficacy of Ketamine HCl Prolonged Release (PR) tablets in participants with pain due to complex regional pain syndrome (CRPS). Additionally, this trial will explore the feasibility of the trial design through dosing compliance, clinical instruments for safety and quality of life measurements, and pharmacokinetic profile.
This study will enroll patients (age 18 to 64 years old) with history of CRPS (diagnosis greater than 6 months prior) at a single academic medical institution in the United States. All participants will be informed about the study and potential risks and will provided written informed consents prior to undergoing any study-related procedures. Health status assessments including physical exams, blood work, urinalysis, EKG and questionnaires to assess quality of life and pain scale measurement will be conducted at the clinic visits. The participants will also keep a daily diary throughout the study to record pain levels, daily blood pressure and any additional pain medication needed. There will be a total of 10 visits: a screening visit (day -28 to -7), clinic visits at day 1 (Baseline), week 2, week 4, week 8, and at the end of study (EOS) visit at 12 weeks. There will be additional telemedicine visits at week 1, week 3, week 5 and at the safety followup visit approximately 4 weeks after the EOS visit. There will also be followup phone call throughout the study to check on compliance and any adverse events. All subjects will start with 40mg BID of Ketamine PR (80 mg/day) on the Baseline visit. The subjects are required to be observed in person for 6 hours following the first dose for any side effects using the Ketamine Side Effects Tools (KSET) - Baseline and Acute Treatment forms \[From: Brooke Short et al. "Development of ketamine side effect tool (KSET) as a reference: J Affect Disord. 2020 April 01; 266: 615-620. doi:10.1016/j.jad.2020.01.120\]. At an in person clinic visit 4 weeks after the Baseline visit, the dose may be increased to 80 mg BID (160 mg/day), using the same observation period as described at the Baseline visit. The study drug dosage will only be increased at this visit if the subject has not experienced adequate pain relief and has not experienced any adverse events. Administration of the study drug will stop at the EOS visit (at 12 weeks after the Baseline visit). Hemodynamic measurements, laboratory results, KSET - Followup form results and examination by the PI/Co-PI will be used throughout the study to assess possible adverse events (AEs). If the subject experiences any Grade 2 AEs, the PI/Co-PI will use clinical expertise and best judgement after determining the subject's level of distress and or discomfort to decide whether the subject will remain at the current dose, decrease the dose or discontinue study drug. If the subject experiences any Grade 3 Adverse Events (AEs), the study drug will be discontinued.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Administration of Ketamine HCl Prolonged Release - 40mg BID
Administration of Ketamine HCl Prolonged Release - 80mg BID
Pain Center, Keck Medical Center of University of Southern California
Los Angeles, California, United States
Average Daily Pain Numerical Rating Scale (ADP NRS)
Average Daily Pain Numerical Rating Scale is a validated, self-reported instrument used to assess average pain intensity level over the past 24 hours. It uses an 11-point (0-10) scale, with 0 being "no pain" and 10 being "worst pain imaginable."
Time frame: Day 1 to week 12
Patient-Reported Outcomes Measurement Information System-2 (PROMIS-29 Profile v2.1)
The PROMIS-29 Profile v2.1 is a validated, self-reported instrument to measure functioning and well-being in 7 categories: physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities and pain interference. There are 4 questions in each of the 7 categories. Each question has five responses with a score from 1 to 5 (1 being best and 5 being worst). For each of these 7 categories, the lowest score is 4; the highest is 20.
Time frame: Day 1 to week 12
Complex Regional Pain Syndrome Severity Scale (CSS)
The CSS Questionnaire assesses changes in Complex Regional Pain Syndrome (CRPS) severity by asking for the presence or absence (score of 1 or 0) of 16 clinically assessed signs and symptoms of CRPS. A higher score is worse, indicate greater CRPS severity (range 0-16).
Time frame: Day 1 to week 12
Patient Global Impression of Change (PGIC)
Patient Global Impression of Change is a validated, self-reported instrument consisting of a 7-point scale (1 through 7) depicting a patient's rating of overall improvement since a certain point in time. The higher PGIC scores, the greater improvement. We will compare the scores at the end of Cycle 1 (1-4 weeks), 2 (4-8 weeks), and 3 (8-12 weeks).
Time frame: Day 1 to week 12
Maximum Plasma concentration [Cmax] of Ketamine
Maximum Plasma concentration \[Cmax\] is the maximum concentration of the drug, Ketamine, in the body, measured in grams/Liter. Blood samples are obtained at Day 2, 4, and 7.
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Time frame: Day 1 to Day 7
Time to Maximum Plasma concentration [Tmax] of Ketamine
Time to Maximum Plasma concentration \[Tmax\] is the time it takes for the drug Ketamine, to reach maximum concentration (Cmax), measured in minutes. Blood samples are obtained at Day 2, 4, and 7.
Time frame: Day 1 to Day 7
Opioid sparing
Participants will record any change in the amount (expressed as MME) and frequency of opioid medications used for treating CRPS pain.
Time frame: Day 1 to week 12
Medication sparing
Participants will record daily use of rescue medication (expressed in mg and number of tablets) for treating CRPS pain. Acetaminophen (up to 3000mg/day) will be offered as rescue medication for breakthrough pain.
Time frame: Day 1 to week 12
Safety of Ketamine HCl PR oral tablets
Number of participants with AEs, with abnormal vital signs, abnormal physical examination parameters; abnormal Electrocardiogram (EKG) parameters; abnormal laboratory parameters
Time frame: Day 1 to 18 weeks