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Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS)

Primary Purpose

Cryptogenic Sensory Polyneuropathy

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Nortriptyline
Duloxetine
Pregabalin
Mexiletine
Sponsored by
University of Kansas Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryptogenic Sensory Polyneuropathy focused on measuring CSPN, neuropathy, pain, pain management

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Barrow Neurological Institute
  • Phoenix Neurological Associates
  • Cedars-Sinai Medical Center
  • California Pacific Medical Center
  • University of California San Francisco
  • University of Colorado Denver Anschutz Campus
  • Colorado Springs Neurological Associates
  • University of Florida - Gainesville
  • University of Florida Health Science Center - Jacksonville
  • University of Miami Miller School of Medicine
  • Neurological Services of Orlando Research
  • University of South Florida
  • NorthShore Neurological Institute
  • Indiana University
  • Mercy Medical Center - Des Moines
  • University of Iowa Hospitals and Clinics
  • Hutchinson Clinic, PA
  • University of Kansas Medical Center
  • Norton Neurology Services
  • Brigham and Women's Hospital
  • University of Michigan
  • Henry Ford Hospital
  • Spectrum Health System
  • University of Minnesota
  • Saint Louis University
  • University of Nebraska Medical Center
  • University of Buffalo School of Medicine and Biomedical Sciences
  • Mount Sinai Beth Israel
  • University of Cincinnati
  • Cleveland Clinic
  • The Ohio State University Wexner Medical Center
  • Oregon Health & Science University
  • Penn State Medical Center
  • Austin Neuromuscular Center
  • Sara Austin, MD, PA
  • Seton Brain and Spine Institute
  • Texas Neurology
  • University of Texas Southwestern
  • University of Texas Health Science Center at Houton
  • Grand Medical Clinic
  • Neurology Clinic of Central Texas
  • University of Texas Health Science Center in San Antonio
  • University of Utah
  • University of Vermont Medical Center
  • University of Virginia
  • Toronto General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Nortriptyline

Duloxetine

Pregabalin

Mexiletine

Arm Description

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.

Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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

Full Information

First Posted
October 6, 2014
Last Updated
June 6, 2018
Sponsor
University of Kansas Medical Center
Collaborators
Patient-Centered Outcomes Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02260388
Brief Title
Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations
Acronym
PAIN-CONTRoLS
Official Title
Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 2014 (Actual)
Primary Completion Date
September 2017 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Kansas Medical Center
Collaborators
Patient-Centered Outcomes Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptogenic Sensory Polyneuropathy
Keywords
CSPN, neuropathy, pain, pain management

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
402 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nortriptyline
Arm Type
Experimental
Arm Description
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.
Arm Title
Duloxetine
Arm Type
Experimental
Arm Description
Duloxetine - 20 mg daily for 1 week, then 40 mg daily for 1 week, then 60 mg daily for the remainder of the study.
Arm Title
Pregabalin
Arm Type
Experimental
Arm Description
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.
Arm Title
Mexiletine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nortriptyline
Intervention Type
Drug
Intervention Name(s)
Duloxetine
Intervention Type
Drug
Intervention Name(s)
Pregabalin
Intervention Type
Drug
Intervention Name(s)
Mexiletine
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
SF12 Health Composite Scores
Description
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.
Time Frame
12 weeks
Title
PROMIS Pain Interference Short Form v1.0 8a T Score
Description
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.
Time Frame
12 weeks
Title
PROMIS Fatigue Short Form v1.0 8a
Description
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.
Time Frame
12 Weeks
Title
PROMIS Sleep Disturbance Short Form v1.0 8a
Description
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
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Barohn, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barrow Neurological Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Phoenix Neurological Associates
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94107
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Colorado Denver Anschutz Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Colorado Springs Neurological Associates
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
University of Florida - Gainesville
City
Gainesville
State/Province
Florida
ZIP/Postal Code
10236
Country
United States
Facility Name
University of Florida Health Science Center - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
University of Miami Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Neurological Services of Orlando Research
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
NorthShore Neurological Institute
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60026
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Mercy Medical Center - Des Moines
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Hutchinson Clinic, PA
City
Hutchinson
State/Province
Kansas
ZIP/Postal Code
67502
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Norton Neurology Services
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Spectrum Health System
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49525
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Facility Name
Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63103
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
University of Buffalo School of Medicine and Biomedical Sciences
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Mount Sinai Beth Israel
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45221
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Austin Neuromuscular Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78703
Country
United States
Facility Name
Sara Austin, MD, PA
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Seton Brain and Spine Institute
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Neurology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75214
Country
United States
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas Health Science Center at Houton
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Grand Medical Clinic
City
Katy
State/Province
Texas
ZIP/Postal Code
77494
Country
United States
Facility Name
Neurology Clinic of Central Texas
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78132
Country
United States
Facility Name
University of Texas Health Science Center in San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05403
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
32809014
Citation
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. Erratum In: JAMA Neurol. 2020 Nov 1;77(11):1453.
Results Reference
derived
PubMed Identifier
27577191
Citation
Brown 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.
Results Reference
derived

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Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations

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