Trans-MAPP Symptom Patterns Study (SPS)

The MAPP Research Network’s second phase (MAPP II ) focused on building from the EPS cohort insights to characterize symptom patterns of change over longer follow-up time and to examine the correlations between symptoms, severity, and risk of change, as well as response to certain therapies. Additional emphasis was also placed on further defining distinct, clinically relevant UCPPS phenotypic subgroups based on pain and urologic and non-urologic symptom profiles. The MAPP II Trans-MAPP Symptom Patterns Study (SPS) enrolled a larger cohort of male and female UCPPS participants (620 consisting of 410 females and 210 males) and assessed them in an extended longitudinal follow-up period of three years. A small cohort (73) of “Healthy Controls” (individuals without UCPPS symptoms) were also enrolled and examined. In addition, a cohort of UCPPS participants originally characterized in the MAPP I EPS protocol (100 of the 620 total) were followed between studies and then enrolled into the MAPP II SPS protocol. This allowed for up to nine years of follow-up for some UCPPS participants.

Summary of MAPP 2 Participant enrollment.

The SPS was conducted by nine Discovery Sites and two Core Sites:

  • Discovery Sites:
    • Cedars-Sinai, Los Angeles, CA
    • Harvard Medical School/Boston Children’s Hospital, Boston, MA
    • Northwestern University, Chicago, IL
    • Queens University, Kingston Ontario, Canada
    • University of California, Los Angeles, Los Angeles, CA
    • University of Iowa, Iowa City, IA
    • University of Michigan, Ann Arbor, MI
    • University of Washington/Washington State University, Seattle, WA
    • Washington University, St. Louis, St. Louis, MO
  • Core Sites:
    • Data Coordinating Core (DCC): University of Pennsylvania, Philadelphia, PA
    • Tissue Analysis and Technology Core (TATC): University of Colorado in Denver, Denver, CO
  • Neuroimaging Core Support Provided by:
    • Neuroimaging Core of the G. Oppenheimer Center for Neurobiology of Stress and Resilience (CNSR) at UCLA

SPS Design and Data/Biosample Domains

The MAPP Network’s MAPP II Symptoms Patterns Study (SPS) was a multi-site cohort study of males and females with UCPPS. It featured a novel run-in period prior to a baseline in-clinic visit, followed by quarterly assessments for up to 36-months. “Healthy” controls participants were also recruited and assessed at baseline and at 6-months.

Eligibility (inclusion and exclusion) criteria for the SPS were intentionally similar to the original EPS criteria. One exception was that former EPS participants could re-enroll in SPS with a current pain/pressure/discomfort score of 0, to provide insight into factors associated with symptom resolution (i.e., since their participation in the EPS). Modified recruitment goals for SPS included 620 UCPPS participants, divided equally among men and women, and 72 healthy controls.

The SPS was designed to provide more comprehensive, integrated cross-modality assessment of clinical, biological and pain sensitivity measures, as well as longer follow-up (144 weeks), compared to the MAPP I EPS (48 weeks). Based on findings from the EPS, additional study features were included in SPS, such as the novel 4-week run-in period with weekly assessments prior to planned “baseline” in-clinic data and biosample/measures collection, performed at the 4-week (fifth) visit. This run-in period allowed an assessment of outcome variability and propensity to adjust for potential “regression-to-the-mean” phenomena. Detailed information about targeted usual‐care therapy and treatment response was also collected to identify UCPPS participants with the potential to preferentially respond to different therapies. Data for the UCPPS participants were obtained at 3-monthly interval contacts over the course of 36 months, with in-clinic deep phenotyping visits conducted at baseline, 6 months, 18 months and 36 months.

During the SPS extensive clinical data assessing urological symptoms, non-urological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. In addition, diverse biospecimens for biomarker and microbiome studies; quantitative sensory testing (QST) data from multiple stimuli; and structural and functional neuroimaging scans, including for a novel natural bladder filling study (“Water Ingestion Protocol”), were obtained during in-clinic visits under the standardized SPS protocol.

Design of MAPP II SPS Study with ATLAS Module

Quarterly on-line symptom data capture via web-based tools for 3 years.


The SPS protocol also included an embedded module, the “Analysis of Therapies during the Longitudinal Assessment of Symptoms (ATLAS)” designed to capture “deep phenotyping” outcomes prior to initiation of and 12 weeks after initiation of select UCPPS therapies. The main goal of the ATLAS study was to identify clinical and biological factors associated with differential response to therapy versus non-response and to allow for assessment of changes of these factors after treatment. Information gained is expected to inform strategies for matching UCPPS phenotypes to targeted therapies in future clinical trial design.

Eligibility for ATLAS was triggered by a UCPPS participant’s treating physician recommending one of seven targeted treatments. These were categorized by mechanisms of action as central (e.g., oral opioids, tricyclic antidepressants, and neuropathic pain agents [gabapentin and pregabalin]) or peripheral (e.g., pelvic floor physical therapy, cystoscopy with hydrodistention, alpha‐adrenergic antagonists (men only), and pentosan polysulfate). See Figure 8 for the design of the SPA ATLAS sub-study.

See About the Mapp Network and Resources tab for the various major study domains assessed in the Trans-MAPP SPS. The specific clinical measures, biological samples, and physical measures collected for each study domain are listed, as well as notations of the main methods and relevant samples used, where applicable (abbreviations are defined). Data and biological samples/measures were similar in both the MAPP I EPS and MAPP II SPS protocols, unless otherwise noted. As with MAPP I, studies using relevant animal models were also performed in MAPP II to complement clinical studies.

For a side-by-side summary of measures collected in the MAPP I EPS and MAPP II SPS Protocols see: PDF

For Additional Information on the Design and Goals of the Trans-MAPP SPS see:

Clemens JQ, Kutch JJ, Mayer EA, The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS). Neurourol Urodyn. 2020 Aug;39(6):1803-1814. doi: 10.1002/nau.24423. Epub 2020 Jun 23. PMID: 32578257; PMC8025696.

For Additional Details on the Trans-MAPP SPS Neuroimaging Study See:

Mawla I, Schrepf A, Ichesco E, Natural bladder filling alters resting brain function at multiple spatial scales: a proof-of-concept MAPP Network Neuroimaging Study. Sci Rep. 2020 Nov 16;10(1):19901. doi: 10.1038/s41598-020-76857-x. PMID: 33199816; PMC7669903.