Cryptogenic Sensory PolyneuropathyPhase 4PAIN-CONTRoLSNCT02260388
Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations
A Phase 4 study testing Nortriptyline, Duloxetine and Pregabalin in people with Cryptogenic Sensory Polyneuropathy, run by University of Kansas Medical Center at 46 sites in 2 countries.
Trial summary
The purpose of this large comparative effectiveness study led by Richard J. Barohn, MD, of the University of Kansas Medical Center, is to learn about the safety and effectiveness of nortriptyline, duloxetine, pregabalin and mexiletine in treating cryptogenic sensory polyneuropathy (CSPN). Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Cryptogenic Sensory Polyneuropathy
- What is being tested?
- Nortriptyline, Duloxetine and Pregabalin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 402 participants
- Where
- 46 sitesin 2 countries
- Study dates
- Oct 2014to Sep 2017
- Phase
- Phase 4
- 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 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of cryptogenic sensory polyneuropathy.
- Likert Pain Score of greater than or equal to 4.
- Must not currently be on nortriptyline, duloxetine, pregabalin or mexiletine or similar class of medication for at least 7 days from baseline study visit.
Who cannot join
- Any medical condition or current medication that would prevent them from taking either nortriptyline, duloxetine, pregabalin or mexiletine.
- Unable to give consent.
- Unable or not willing to comply with the study.
- Other causes for polyneuropathy.
Trial locations and contacts
46 sites in 2 countries.
46 sites in 2 countries
United States45 sites
University of Michigan
Ann Arbor, Michigan, 48105
University of Colorado Denver Anschutz Campus
Aurora, Colorado, 80045
Austin Neuromuscular Center
Austin, Texas, 78703
Sara Austin, MD, PA
Austin, Texas, 78705
Seton Brain and Spine Institute
Austin, Texas, 78705
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Buffalo School of Medicine and Biomedical Sciences
Buffalo, New York, 14203
University of Vermont Medical Center
Burlington, Vermont, 05403
University of Virginia
Charlottesville, Virginia, 22908
University of Cincinnati
Cincinnati, Ohio, 45221
Cleveland Clinic
Cleveland, Ohio, 44195
Colorado Springs Neurological Associates
Colorado Springs, Colorado, 80907
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Texas Neurology
Dallas, Texas, 75214
University of Texas Southwestern
Dallas, Texas, 75390
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Henry Ford Hospital
Detroit, Michigan, 48202
University of Florida - Gainesville
Gainesville, Florida, 10236
NorthShore Neurological Institute
Glenview, Illinois, 60026
Spectrum Health System
Grand Rapids, Michigan, 49525
Penn State Medical Center
Hershey, Pennsylvania, 17033
University of Texas Health Science Center at Houton
Houston, Texas, 77030
Hutchinson Clinic, PA
Hutchinson, Kansas, 67502
Indiana University
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Florida Health Science Center - Jacksonville
Jacksonville, Florida, 32209
University of Kansas Medical Center
Kansas City, Kansas, 66160
Grand Medical Clinic
Katy, Texas, 77494
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Norton Neurology Services
Louisville, Kentucky, 40207
University of Miami Miller School of Medicine
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55414
Neurology Clinic of Central Texas
New Braunfels, Texas, 78132
Mount Sinai Beth Israel
New York, New York, 10029
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Neurological Services of Orlando Research
Orlando, Florida, 32806
Barrow Neurological Institute
Phoenix, Arizona, 85013
Phoenix Neurological Associates
Phoenix, Arizona, 85018
Oregon Health & Science University
Portland, Oregon, 97239
University of Utah
Salt Lake City, Utah, 84112
University of Texas Health Science Center in San Antonio
San Antonio, Texas, 78229
California Pacific Medical Center
San Francisco, California, 94107
University of California San Francisco
San Francisco, California, 94143
Saint Louis University
St Louis, Missouri, 63103
University of South Florida
Tampa, Florida, 33612
About this study
Official title: Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS)
The purpose of this large comparative effectiveness study led by Richard J. Barohn, MD, of the University of Kansas Medical Center, is to learn about the safety and effectiveness of nortriptyline, duloxetine, pregabalin and mexiletine in treating cryptogenic sensory polyneuropathy (CSPN).
Read the detailed description
The goal of this research project is to find the best drug for the treatment of pain in patients with CSPN. While the pharmaceutical industry has focused attention on drugs for treating diabetic sensory neuropathy (DSPN), and two drugs are now FDA approved, there have not been any prospective trials in CSPN. And, because there are no studies with CSPN patients, insurance carriers often reject authorizing prescriptions for some drugs for patients with CSPN.
There are four drugs that will be tested in this study: nortriptyline, duloxetine, pregabalin and mexiletine. These drugs are not approved by the FDA for the treatment of CSPN and are considered "investigational" in this study.
There are two periods in this study: Screening/Baseline and Study Drug. During the Screening/Baseline period the researchers will determine eligibility for potential subjects. During the second period, eligible patients who consented to participate will take the study drug. Participants will be randomized to receive one of the four drugs in this study. Participants will know which drug they are taking. Participants will not be allowed to switch groups and receive a different drug during the study.
This study uses an adaptive study design. This means the study can enroll less participants and provide better conclusions. The study design allows the researchers the ability to make changes to the approach of the study or to stop the study early if there are strong results.
- Conditions
- Cryptogenic Sensory Polyneuropathy
- Being tested
- Nortriptyline, Duloxetine, Pregabalin, Mexiletine
- Keywords
- CSPN, neuropathy, pain, pain management
- Medical subject headings
- Pain, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NortriptylineDrug
DuloxetineDrug
PregabalinDrug
MexiletineDrug
| Study group | Role | What they receive |
|---|---|---|
| Nortriptyline | Experimental | Nortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. Receives: Drug: Nortriptyline |
| Duloxetine | Experimental | Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. Receives: Drug: Duloxetine |
| Pregabalin | Experimental | Pregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. Receives: Drug: Pregabalin |
| Mexiletine | Experimental | Mexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. Receives: Drug: Mexiletine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit
The final outcome of the study is a combination of two endpoints, efficacy and quit or treatment discontinuation rates. The first endpoint was a patient responder-defined measure of efficacy. A patient was deemed efficacious if a 50% or more reduction was observed in the Likert pain-scale from the baseline visit to the 12 week visit (i.e. 6 at baseline to 3 or less at week 12). The second endpoint was the observed percentage of patients who discontinued treatment prior to the last follow up visit for any reason or were lost to follow up. The utility function, which combines efficacy and quit rates, was used to drive the adaptive randomization, stopping criteria, and final analysis conclusions.
Measured: 12 weeks
Secondary outcomes (4)
SF12 Health Composite Scores
SF-12v2® Health Survey Standard The Optum™ SF-12v2® Health Survey is a shorter version of the SF-36v2® Health Survey that uses just 12 questions to measure functional health and well-being from the patient's point of view.
Survey provides psychometrically-based physical component summary (PCS) and mental component summary (MCS) scores.
Scores are calibrated so that 50 is the average score or norm, standard deviation = 10.
Higher scores indicate better health for both mental and physical component summary scores.
Measured: 12 weeks
PROMIS Pain Interference Short Form v1.0 8a T Score
Higher scores for pain interference represents worse outcome (more pain interference) T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population.
Measured: 12 weeks
PROMIS Fatigue Short Form v1.0 8a
Higher scores for fatigue represents worse outcome (more fatigue). T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population.
Measured: 12 Weeks
PROMIS Sleep Disturbance Short Form v1.0 8a
Higher scores for sleep disturbance represents worse outcome (more sleep disturbance).
T-score metric: 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
On the T-score metric: A score of 40 is one SD lower than the mean of the reference population; A score of 60 is one SD higher than the mean of the reference population.
Higher scores equals more of the concept being measured
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionSep 2017
- Study completionSep 2017
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 (2)Papers the sponsor has linked to this study.
- Other trials for Cryptogenic Sensory PolyneuropathyStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 402 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Sponsor
- Investigators
- Richard Barohn, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02260388
- Sponsor's protocol ID
- STUDY00001500
- Other IDs
- PCORI-1306-02496
- Acronym
- PAIN-CONTRoLS
- Status last verified
- Jun 2018
- First submitted
- 6 Oct 2014
- Last updated
- 6 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Barohn RJ, Gajewski B, Pasnoor M, Brown A, Herbelin LL, Kimminau KS, Mudaranthakam DP, Jawdat O, Dimachkie MM; Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS) Study Team; Iyadurai S, Stino A, Kissel J, Pascuzzi R, Brannagan T, Wicklund M, Ahmed A, Walk D, Smith G, Quan D, Heitzman D, Tobon A, Ladha S, Wolfe G, Pulley M, Hayat G, Li Y, Thaisetthawatkul P, Lewis R, Biliciler S, Sharma K, Salajegheh K, Trivedi J, Mallonee W, Burns T, Jacoby M, Bril V, Vu T, Ramchandren S, Bazant M, Austin S, Karam C, Hussain Y, Kutz C, Twydell P, Scelsa S, Kushlaf H, Wymer J, Hehir M, Kolb N, Ralph J, Barboi A, Verma N, Ahmed M, Memon A, Saperstein D, Lou JS, Swenson A, Cash T. Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial. JAMA Neurol. 2021 Jan 1;78(1):68-76. doi: 10.1001/jamaneurol.2020.2590.
PubMed 32809014Brown AR, Gajewski BJ, Aaronson LS, Mudaranthakam DP, Hunt SL, Berry SM, Quintana M, Pasnoor M, Dimachkie MM, Jawdat O, Herbelin L, Barohn RJ. A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization. Trials. 2016 Aug 31;17(1):428. doi: 10.1186/s13063-016-1544-5.
PubMed 27577191
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS)
- ClinicalTrials.gov ID
- NCT02260388
- Acronym / sponsor ID
- PAIN-CONTRoLS / STUDY00001500
- Conditions
- Cryptogenic Sensory Polyneuropathy
- Keywords
- CSPN, neuropathy, pain, pain management
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 402 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- Oct 2014 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 9 Oct 2014 (estimated)
- Results
- Posted 6 Jul 2018
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 large comparative effectiveness study led by Richard J. Barohn, MD, of the University of Kansas Medical Center, is to learn about the safety and effectiveness of nortriptyline, duloxetine, pregabalin and mexiletine in treating cryptogenic sensory polyneuropathy (CSPN).
Detailed description
The goal of this research project is to find the best drug for the treatment of pain in patients with CSPN. While the pharmaceutical industry has focused attention on drugs for treating diabetic sensory neuropathy (DSPN), and two drugs are now FDA approved, there have not been any prospective trials in CSPN. And, because there are no studies with CSPN patients, insurance carriers often reject authorizing prescriptions for some drugs for patients with CSPN.
There are four drugs that will be tested in this study: nortriptyline, duloxetine, pregabalin and mexiletine. These drugs are not approved by the FDA for the treatment of CSPN and are considered "investigational" in this study.
There are two periods in this study: Screening/Baseline and Study Drug. During the Screening/Baseline period the researchers will determine eligibility for potential subjects. During the second period, eligible patients who consented to participate will take the study drug. Participants will be randomized to receive one of the four drugs in this study. Participants will know which drug they are taking. Participants will not be allowed to switch groups and receive a different drug during the study.
This study uses an adaptive study design. This means the study can enroll less participants and provide better conclusions. The study design allows the researchers the ability to make changes to the approach of the study or to stop the study early if there are strong results.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Nortriptyline | Experimental | Drug: NortriptylineNortriptyline - 25 mg daily for 1 week at bedtime, then 50 mg daily at bedtime for 1 week, then 75 mg daily at bedtime for the remainder of the study. |
| Duloxetine | Experimental | Drug: DuloxetineDuloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study. |
| Pregabalin | Experimental | Drug: PregabalinPregabalin - 100 mg at bedtime for 1 week, then 100 mg 2 times per day for 1 week, then 100 mg 3 times per day for the remainder of the study. |
| Mexiletine | Experimental | Drug: MexiletineMexiletine - 200 mg at bedtime for 1 week, then 200 mg 2 times per day for 1 week, then 200 mg 3 times per day for the remainder of the study. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of cryptogenic sensory polyneuropathy.
- Likert Pain Score of greater than or equal to 4.
- Must not currently be on nortriptyline, duloxetine, pregabalin or mexiletine or similar class of medication for at least 7 days from baseline study visit.
Key exclusion criteria (4 listed)
- Any medical condition or current medication that would prevent them from taking either nortriptyline, duloxetine, pregabalin or mexiletine.
- Unable to give consent.
- Unable or not willing to comply with the study.
- Other causes for polyneuropathy.
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 |
|---|---|---|
| Nortriptyline | Drug | Nortriptyline |
| Duloxetine | Drug | Duloxetine |
| Pregabalin | Drug | Pregabalin |
| Mexiletine | Drug | Mexiletine |
Primary outcome
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit
Time frame: 12 weeks
The final outcome of the study is a combination of two endpoints, efficacy and quit or treatment discontinuation rates. The first endpoint was a patient responder-defined measure of efficacy. A patient was deemed efficacious if a 50% or more reduction was observed in the Likert pain-scale from the baseline visit to the 12 week visit (i.e. 6 at baseline to 3 or less at week 12). The second endpoint was the observed percentage of patients who discontinued treatment prior to the last follow up visit for any reason or were lost to follow up. The utility function, which combines efficacy and quit rates, was used to drive the adaptive randomization, stopping criteria, and final analysis conclusions.
4 secondary outcomes
SF12 Health Composite Scores
Time frame: 12 weeks
PROMIS Pain Interference Short Form v1.0 8a T Score
Time frame: 12 weeks
PROMIS Fatigue Short Form v1.0 8a
Time frame: 12 Weeks
PROMIS Sleep Disturbance Short Form v1.0 8a
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32809014Barohn RJ, Gajewski B, Pasnoor M, Brown A, Herbelin LL, Kimminau KS, Mudaranthakam DP, Jawdat O, Dimachkie MM; Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS) Study Team; Iyadurai S, Stino A, Kissel J, Pascuzzi R, Brannagan T, Wicklund M, Ahmed A, Walk D, Smith G, Quan D, Heitzman D, Tobon A, Ladha S, Wolfe G, Pulley M, Hayat G, Li Y, Thaisetthawatkul P, Lewis R, Biliciler S, Sharma K, Salajegheh K, Trivedi J, Mallonee W, Burns T, Jacoby M, Bril V, Vu T, Ramchandren S, Bazant M, Austin S, Karam C, Hussain Y, Kutz C, Twydell P, Scelsa S, Kushlaf H, Wymer J, Hehir M, Kolb N, Ralph J, Barboi A, Verma N, Ahmed M, Memon A, Saperstein D, Lou JS, Swenson A, Cash T. Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial. JAMA Neurol. 2021 Jan 1;78(1):68-76. doi: 10.1001/jamaneurol.2020.2590.
- Derived from this study: PubMed 27577191Brown AR, Gajewski BJ, Aaronson LS, Mudaranthakam DP, Hunt SL, Berry SM, Quintana M, Pasnoor M, Dimachkie MM, Jawdat O, Herbelin L, Barohn RJ. A Bayesian comparative effectiveness trial in action: developing a platform for multisite study adaptive randomization. Trials. 2016 Aug 31;17(1):428. doi: 10.1186/s13063-016-1544-5.
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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.
Richard Barohn, MD principal investigator
University of Kansas Medical Center
46 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nortriptyline, Duloxetine and Pregabalin in people with Cryptogenic Sensory Polyneuropathy, run by University of Kansas Medical Center at 46 sites in 2 countries.
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 3 inclusion and 4 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 6 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 6 Jul 2018). 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?
Co-Primary Measures: Percent of Patients With at Least a 50% Decrease in Likert Pain Scale From Baseline to Week 12 Follow Up and Percent of Patients That Quit (time frame: 12 weeks). 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 NCT02260388, which also lists 2 linked publications.
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 6 Jul 2018.