Complex Regional Pain SyndromesPhase 2NCT06419985
Ketamine HCl Prolonged Release Oral Tablets for CRPS
A Phase 2 study testing 80mg/day Ketamine HCl Prolonged Release and 160mg/day Ketamine HCl Prolonged Release in people with Complex Regional Pain Syndromes, run by University of Southern California at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Complex Regional Pain Syndromes
- What is being tested?
- 80mg/day Ketamine HCl Prolonged Release and 160mg/day Ketamine HCl Prolonged Release
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Jul 2029
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female participants between 18 and 64 years of age, inclusive, at Screening Visit.
- Participants with a documented history of CRPS of at least 6 months at Visit 1.
- At least one sign in two of the categories of The Budapest Criteria for CRPS to support the diagnosis of CRPS.
- Stable individual regular standard treatment regimen for CRPS pain, i.e., no change in drug and non-drug treatments for at least 4 weeks prior to Screening Visit and anticipated to remain stable throughout the study.
- No surgery, denervation procedures or neural blockade within 1 month of Screening Visit.
- Participants on ketamine therapy at Screening Visit must agree to discontinue use for at least 14 days prior to the Baseline Observation Period.
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- Agree to discontinue any prohibited medications within prior to 14 days of the Baseline Observation Period and for the duration of the study.
- Average daily CRPS pain intensity score in the affected limb of ≥5 and ≤9 on an 11-point (0-10) NRS averaged over 7 days prior to Baseline Visit (Visit 1). This will be based on completion of at least 5 daily pain diary entries during the week prior to Visit 1, with no more than one 24-hour pain intensity score of zero or more than one 24-hour pain intensity score of 10.
- Participants willing and able (e.g., mental and physical condition) to participate in all aspects of the trial, including use of medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing signed written informed consent at Screening Visit.
- For persons of reproductive potential: use of highly effective contraception (females: barrier (condom, diaphragm, sponge, cervical cap) and/or oral, implantable rod, or intrauterine device birth control; males: barrier (condom)) for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 weeks after the end of study intervention administration.
Who cannot join
- Known or suspected cardiovascular disease, arrythmias, and/or respiratory issues.
- Abnormal EKG results, abnormal blood pressure (SBP <90 or ≥ 140; DBP <50 or ≥ 90) and/or heart rates (<50 or >110).
- Known or suspected psychotic illness or neurologic disease.
- Known or suspected elevated intraocular and/or intracranial pressure.
- Known or suspected renal or urologic conditions or symptoms (i.e., bladder pain syndrome, interstitial cystitis), and/or abnormal baseline urinalysis results.
- Known or suspected hyperthyroidism.
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- Allergy, hypersensitivity, or intolerance to ketamine or any of the investigational product excipients.
- Participants receiving opioids ≥30 mg/day morphine milligram equivalents (MME), whether as part of their individual standard treatment regimen for CRPS pain or in context with any other indication, within the last two weeks prior to Visit 1.
- Positive urine screen for any of the following: cocaine, amphetamine, methamphetamine, PCP, opioids, THC (other than medication used for individual standard treatment of pain) at Visit 1.
- Known or suspected acute or chronic alcoholism, delirium tremens, or toxic psychosis.
- Meet DSM-5 criteria for current or past substance use disorder within the last 5 years for any psychoactive substances other than nicotine or caffeine.
- Known hepatic dysfunction or serious liver disease, including presence of aspartate aminotransferase (AST) levels ≥ 2 X upper limit of normal and/or alanine aminotransferase (ALT) levels ≥ 2 X upper limit of normal and/or total bilirubin ≥ 1.5 X upper limit of normal
- Abnormal urinalysis, urine culture or abnormal creatinine
- Evidence of moderate or severe renal impairment (CRCL <60 ml/min) or participants with renal failure who are on any form of dialysis.
- Current or previous history of seizures.
- A positive pregnancy test/confirmed pregnancy test at the screening or baseline visit.
- If Ask Suicide-Screening Questionnaire (ASQ) is positive at Grade 2 (moderate), subject will be excluded.
- Any other condition of the patient that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize participant's safety, compliance or adherence to protocol requirements.
- Previous enrollment in this trial or participation in any other clinical trial within the past 30 days prior to enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Pain Center, Keck Medical Center of University of Southern California
Los Angeles, California, 90033
About this study
Official title: A Phase 2 Single-arm, Open Label Clinical Trial to Evaluate the Efficacy of Ketamine HCl Prolonged Release Tablets in Participants With Complex Regional Pain Syndrome
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.
Read the detailed description
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.
- Conditions
- Complex Regional Pain Syndromes
- Being tested
- 80mg/day Ketamine HCl Prolonged Release, 160mg/day Ketamine HCl Prolonged Release
- Keywords
- CRPS
- Medical subject headings
- Complex Regional Pain Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
80mg/day Ketamine HCl Prolonged ReleaseDrug
Also called 80mg Ketamine PR
Administration of Ketamine HCl Prolonged Release - 40mg BID
160mg/day Ketamine HCl Prolonged ReleaseDrug
Also called 160mg Ketamine PR
Administration of Ketamine HCl Prolonged Release - 80mg BID
| Study group | Role | What they receive |
|---|---|---|
| 80mg Ketamine HCl PR | Experimental | One 40mg tablet of Ketamine HCl PR twice a day, which may be increased to two 40mg tablets Ketamine HCl PR twice a day at week 4 if subject does not experience adequate pain relief. Receives: Drug: 80mg/day Ketamine HCl Prolonged Release; Drug: 160mg/day Ketamine HCl Prolonged Release |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: Day 1 to week 12
Secondary outcomes (8)
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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Day 1 to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2024
- Study startJan 2027 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJul 2029 (estimated)
Why it stopped: Difficulty clearing through the FDA
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complex Regional Pain SyndromesStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Richeimer, University of Southern California
- Investigators
- Steven Richeimer, MD, Principal investigator, Keck Medical Center of USC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06419985
- Sponsor's protocol ID
- 23015-0001
- Status last verified
- Jul 2026
- First submitted
- 6 May 2024
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Single-arm, Open Label Clinical Trial to Evaluate the Efficacy of Ketamine HCl Prolonged Release Tablets in Participants With Complex Regional Pain Syndrome
- ClinicalTrials.gov ID
- NCT06419985
- Acronym / sponsor ID
- 23015-0001
- Conditions
- Complex Regional Pain Syndromes
- Keywords
- CRPS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Difficulty clearing through the FDA
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Jan 2027 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 17 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 80mg Ketamine HCl PR | Experimental | Drug: 80mg/day Ketamine HCl Prolonged Release, Drug: 160mg/day Ketamine HCl Prolonged ReleaseOne 40mg tablet of Ketamine HCl PR twice a day, which may be increased to two 40mg tablets Ketamine HCl PR twice a day at week 4 if subject does not experience adequate pain relief. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Male and female participants between 18 and 64 years of age, inclusive, at Screening Visit.
- Participants with a documented history of CRPS of at least 6 months at Visit 1.
- At least one sign in two of the categories of The Budapest Criteria for CRPS to support the diagnosis of CRPS.
- Stable individual regular standard treatment regimen for CRPS pain, i.e., no change in drug and non-drug treatments for at least 4 weeks prior to Screening Visit and anticipated to remain stable throughout the study.
- No surgery, denervation procedures or neural blockade within 1 month of Screening Visit.
Key exclusion criteria (19 listed)
- Known or suspected cardiovascular disease, arrythmias, and/or respiratory issues.
- Abnormal EKG results, abnormal blood pressure (SBP <90 or ≥ 140; DBP <50 or ≥ 90) and/or heart rates (<50 or >110).
- Known or suspected psychotic illness or neurologic disease.
- Known or suspected elevated intraocular and/or intracranial pressure.
- Known or suspected renal or urologic conditions or symptoms (i.e., bladder pain syndrome, interstitial cystitis), and/or abnormal baseline urinalysis results.
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 |
|---|---|---|
| 80mg/day Ketamine HCl Prolonged ReleaseAlso: 80mg Ketamine PRAdministration of Ketamine HCl Prolonged Release - 40mg BID | Drug | 80mg Ketamine HCl PR |
| 160mg/day Ketamine HCl Prolonged ReleaseAlso: 160mg Ketamine PRAdministration of Ketamine HCl Prolonged Release - 80mg BID | Drug | 80mg Ketamine HCl PR |
Primary outcome
Average Daily Pain Numerical Rating Scale (ADP NRS)
Time frame: Day 1 to week 12
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."
8 secondary outcomes
Patient-Reported Outcomes Measurement Information System-2 (PROMIS-29 Profile v2.1)
Time frame: Day 1 to week 12
Complex Regional Pain Syndrome Severity Scale (CSS)
Time frame: Day 1 to week 12
Patient Global Impression of Change (PGIC)
Time frame: Day 1 to week 12
Maximum Plasma concentration [Cmax] of Ketamine
Time frame: Day 1 to Day 7
Time to Maximum Plasma concentration [Tmax] of Ketamine
Time frame: Day 1 to Day 7
Opioid sparing
Time frame: Day 1 to week 12
Medication sparing
Time frame: Day 1 to week 12
Safety of Ketamine HCl PR oral tablets
Time frame: Day 1 to 18 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Sammy Al Mukhaizeem, et al. Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic painLink provided by the sponsor.
- Megan Dutton, et al. Oral ketamine may offer a solution to the ketamine conundrumLink provided by the sponsor.
- Mark C. Enarson, et al. Clinical Experience with Oral KetamineLink provided by the sponsor.
- Glue, et al. Extended-release ketamine tablets for treatment-resistant depression: A randomized placebo-controlled phase 2 trialLink provided by the sponsor.
- Hasan, M. et al. Chiral Pharmacokinetics and Metabolite Profile of Prolonged-release Ketamine Tablets in Healthy Human SubjectsLink provided by the sponsor.
- Naim Zaki, et al. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 studyLink provided by the sponsor.
- 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.
Steven Richeimer, MD principal investigator
Keck Medical Center of USC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 80mg/day Ketamine HCl Prolonged Release and 160mg/day Ketamine HCl Prolonged Release in people with Complex Regional Pain Syndromes, run by University of Southern California 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 10 inclusion and 19 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: paused, as of the sponsor's last update on 27 Jul 2026. 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 phase mean?
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?
Results are not available in the source record.
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?
Average Daily Pain Numerical Rating Scale (ADP NRS) (time frame: Day 1 to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jul 2026.