Lessons Learned from the MAPP Research Network J. Quentin Clemens, - - PowerPoint PPT Presentation

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Lessons Learned from the MAPP Research Network J. Quentin Clemens, - - PowerPoint PPT Presentation

Nov 09, 2022 297 likes •599 views

Lessons Learned from the MAPP Research Network J. Quentin Clemens, MD, FACS, MSCI MAPP Research Network Chair Professor of Urology University of Michigan Medical Center Ann Arbor, MI USA What is MAPP? The Multidisciplinary Approach to the

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  • J. Quentin Clemens, MD, FACS, MSCI

MAPP Research Network Chair Professor of Urology University of Michigan Medical Center Ann Arbor, MI USA

Lessons Learned from the MAPP Research Network

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MAPP Research Network

What is MAPP?

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Multi-institutional, collaborative network NIH Funding Dedicated to the study of … IC/BPS and CP/CPPS ... Urologic Chronic Pelvic Pain Syndrome (UCPPS)

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MAPP Research Network

  • Lack of clinical advancement in the field of UCPPS
  • Little Interdisciplinary work
  • New literature (and clinical experience) suggesting

that UCPPS likely represents a heterogeneous group

  • f patients, many of whom suffer from pain that

reaches far beyond the urogenital system.

Why Do We Need MAPP?

Better Phenotyping = Better Outcomes

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MAPP Research Network

MAPP Organization

w Recruitment Discovery Sites (Urologic and Non-Urologic Expertise)

  • Northwestern University
  • UCLA
  • University of Iowa
  • University of Michigan
  • University of Washington
  • Washington University in St. Louis

w Data Coordinating Center – University of Pennsylvania w Tissue and Technology Core – University of Colorado w NIDDK w Specialized Discovery Sites

  • Boston Children’s, Queens University, Cedars Sinai
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MAPP Research Network

MAPP Research Network Sites

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MAPP Research Network

  • To better understand the treated natural history of

UCPPS.

  • To identify clinical factors and research measurements

that will define clinically relevant sub-groups of these patients for future clinical trials.

  • Address underlying disease pathophysiology and

natural history using patient cohorts, biospecimens and animal models

Broad Goals of the MAPP Network

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MAPP Research Network

MAPP Subject Recruitment

w Broad inclusion criteria

  • Diagnosis of IC/BPS or CP/CPPS
  • Age 18+
  • Standard exclusions (pelvic malignancy, neurologic disorders, etc)
  • Target was 50% with symptoms < 2 years

w Controls

  • Asymptomatic
  • ‘Positive’ controls – with fibromyalgia, irritable bowel syndrome,

chronic fatigue syndrome

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MAPP Research Network

Baseline Data

wDemographics wMedical History wUrologic Symptoms wPain Symptoms wPsychosocial Symptoms wPhysical Examination wBiospecimens

  • urine, blood, DNA

wNeuroimaging wQuantitative Sensory Testing

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MAPP Research Network

MAPP Study Flow

All Subjects Baseline In-Clinic Visit Intensive Phenotyping UCPPS Subjects Only 6 and 12 month In-Clinic Visits Bi-Weekly Internet Assessments All Subjects Additional trans-MAPP and Site- Specific Studies Subjects Recruited at Discovery Sites

Regular Treatments Allowed

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MAPP Research Network

MAPP Cohorts By Sex

Sex UCPPS Healthy Controls Positive Controls Total Male 191 182 44 417 Female 233 233 156 622 Total 424 415 200 1,039

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MAPP Research Network

MAPP Epidemiology - Phenotyping Study

Study Subjects

w Demographic and clinical characteristics are similar to other cohorts in the literature

  • Men => mean age 46.8yrs, mean symptom duration 7.8 yrs, mean CPSI score

22.5

  • Women => mean age 40.5yrs, mean symptom duration 9.1 yrs, mean ICSI

score 10.8

w Biweekly Internet-based assessments for 12 months

  • 83% missed no more than 3 of the planned 26 contacts!

Clemens et al. J Urol 2015;193:1554.

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MAPP Research Network

MAPP Epidemiology-Phenotyping Study

Location of Reported Pain from Body Map

w Pelvic Pain Only

  • Areas 14, 15 or 16
  • 26%

w Pelvic Pain and Beyond

  • 74%
  • “Centralized” phenotype
  • More severe UCPPS symptoms
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MAPP Research Network

MAPP Epidemiology-Phenotyping Study Findings

UCPPS and Other Pain Syndromes

w Psychosocial symptoms were similar in UCPPS subjects and “positive” controls with fibromyalgia, IBS, chronic fatigue syndrome w Chronic overlapping pain conditions (fibromyalgia, IBS, chronic fatigue syndrome) in UCPPS patients

  • 43% females, 30% males
  • More severe UCPPS symptoms
  • Worse QOL
  • More psychosocial symptoms

Krieger et al. J Urol 2015;193:1254.

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MAPP Research Network

MAPP Epidemiology-Phenotyping Study Findings

Bladder-Sensitivity Phenotype

w Urinary urgency due to pain/ pressure/discomfort w Pain that worsens with bladder filling w One or more positive response:

  • 88% of women
  • 75% of men
  • Suggests overlap in symptoms between IC/BPS and CP/CPPS

w Bladder hypersensitivity associated with:

  • More severe UCPPS symptoms
  • More non-urologic pain
  • Worse QOL

Lai et al. J Urol, 2016

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MAPP Research Network

MAPP Epidemiology-Phenotyping Study Findings

Symptom Assessment

w Baseline questionnaire responses - two factors provided the best psychometric description of items:

  • Pain symptoms
  • Urinary symptoms

w Equivalent results in men and women w Longitudinal analysis – pain and urinary symptoms track differently w These findings suggest that pain and urinary symptoms should be examined separately, rather than using a ‘composite’ symptom score.

Griffith et al. J Urol, 2016

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MAPP Research Network

Pain Severity Functional Clusters: Absolute Change

Cluster Symptom Pattern Total (Percent) 1 Improving 87 (20.5%) 2 Stable 257 (60.6%) 3 Worsening 80 (18.9%) Overall 424 (100.0%)

Naliboff et al. J Urol, 2017

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MAPP Research Network

Urinary Severity Functional Clusters: Absolute Change

Cluster Symptom Pattern Total (Percent) 1 Improving 83(19.6%) 2 Stable 288 (67.9%) 3 Worsening 53(12.5%) Overall 424 (100.0%)

Naliboff et al. J Urol, 2017

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MAPP Research Network

Change in Symptoms Over 12 Months

Significant predictors of better outcomes included: Ø Higher baseline symptom severity Ø Less widespread pain and non-urologic symptoms Ø CMSI and body map Ø Better overall physical health

  • SF-12 physical, PROMIS sleep, PROMIS fatigue

Ø Better overall mental health

  • SF-12 mental, pain catastrophizing, perceived stress

Naliboff et al. J Urol, 2017

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MAPP Research Network

Change in Symptoms Over 12 Months

No impact: Ø Age, sex, symptom duration, anxiety, depression Ø CMSI and body map Ø Better overall physical health

  • SF-12 physical, PROMIS sleep, PROMIS fatigue

Ø Better overall mental health

  • SF-12 mental, pain catastrophizing, perceived stress

Naliboff et al. J Urol, 2017

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MAPP Research Network

MAPP Epidemiology-Phenotyping Study Findings

Symptom Flares

w Females reported 507 symptom flares, Males reported 297 flares w 95% reported at least one flare

  • 1-4 flares => 26%
  • 5-9 flares => 28%
  • 10+ flares => 41%

w More common with ‘centralized’ phenotype and with more severe bladder symptoms (‘bladder’ phenotype) w Focus groups

  • Flares vary in symptom type, severity and duration (minutes to days)
  • Unpredictable
  • Lead to social avoidance and isolation

Sutcliffe S et al. Int Urogynecol J 2015;26:1047

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MAPP Research Network

Regression to the Mean

w Early symptom changes (regression to the mean) were common and impacted the assessment of symptom trajectory over time.

Improved No Change Worse Week 0-48 Data 25.2-37.7% 56.8-68.9% 5.4-5.9% Week 4-48 Data 15.0-24.8% 65.8-78.5% 6.1-9.4%

Stephens-Shields et al. J Urol 2016

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MAPP Research Network

MAPP Epidemiology-Phenotyping Study Findings

Summary

w Clinical phenotyping of UCPPS patients should focus on at least 3 important factors:

  • Pain localization (presence of pain outside of the pelvis)
  • Presence of chronic overlapping pain conditions
  • Bladder hypersensitivity

w We should consider abandoning ‘total symptom scores’ and instead utilize dual outcomes (pain symptoms, urinary symptoms)

Griffith et al. J Urol, 2016

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MAPP Research Network

MAPP Study Findings

Pain Testing

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MAPP Research Network

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MAPP Research Network

Pain Sensitivity

Ø Positive Controls > Healthy Controls Ø UCPPS > Healthy Controls Ø Positive Controls = UCPPS

Increased pain sensitivity was associated with:

Ø Increased UCPPS symptom severity Ø More Flares Ø Less likelihood of symptom improvement

Pain Testing - Summary Findings

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MAPP Research Network

MAPP Network Neuroimaging Highlights

w Resting State Functional Connectivity Predicts Longitudinal Symptom Change in UCPPS

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MAPP Research Network

MAPP Network Neuroimaging Highlights

Kairys et al., 2015 Kilpatrick et al., 2014 Woodworth et al., 2015 RS-fMRI T1 DTI

Region specific to pelvic floor

Asavasopon et al., 2014 Rana et al., 2015

UCPPS/Control Differences:

Kutch et al., 2015

w Explain pathophysiology

MAPP Network Neuroimaging Highlights

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MAPP Research Network

w Structural and functional differences exist in UCPPS patients with widespread pain. w These findings match up with fibromyalgia patients.

MAPP Network Neuroimaging Publication Highlights cont’

MAPP Network Neuroimaging Highlights

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MAPP Research Network

MAPP Study

Future Directions

w Second phase of the MAPP Research Network: 2015 to 2019 w Assessment of symptom patterns and corresponding biologic change through longer follow-up w Evaluation of promising candidate biomarkers w Longitudinal neuroimaging and quantitative pain testing w In-depth assessment of treatment response w Identification of clinically relevant UCPPS patient sub-groups

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MAPP Research Network

www.mappnetwork.org