The University of Michigan MAPP Discovery Site has provided significant leadership to the first phase of the Multidisciplinary Approach to Chronic Pelvic Pain (MAPP) effort to study urinary chronic pelvic pain syndromes (UCPPS). We provided the initial (Clauw) and current (Clemens) network chairs, and leadership in phenotyping (Williams), quantitative sensory testing (Harte) and neuroimaging (Harris). In addition, we were an excellent recruitment site for the MAPP, with total numbers of participants enrolled (186) and retention of participants (92%) amongst the highest of any site. We propose to similarly provide organizational and scientific leadership in Phase II of the MAPP. In addition to the performance of the UCPPS Symptom Pattern Study, we propose three additional aims we believe bring innovative research methods and expertise to the broader trans-MAPP efforts.
These aims are: 1) To continue our effective participation in trans-MAPP studies, including the UCPPS Symptom Patterns Study. 2) To perform an Interventional Phenotyping study that can either be immediately adopted trans-MAPP or serve as a pilot for a broader trans-MAPP effort in Phase II. This will be the first study ever to hypothesize that symptom profiles, quantitative sensory testing and functional neuroimaging can be used to identify subsets of UCPPS patients (endo-phenotypes) that have differing underlying mechanisms and thus will respond to different treatments. In particular, we hypothesize that we can predict differential responsiveness to a UCPPS treatment thought to work primarily via central mechanisms (a tricyclic compound) vs. one that is primarily though to work via more peripheral mechanisms (a NSAID). 3) To provide guidance and expertise for trans-MAPP genetic efforts. We propose to bring several colleagues with internationally recognized expertise in genetics into the MAPP to help inform and guide our trans-MAPP efforts, including the best strategies to use to analyze both Phase I and II samples. We hypothesize that genetic variations will facilitate the identification of endo-phenotypes as well as the longitudinal course of UCPPS. 4) To provide a broader and more comprehensive set of quantitative sensory testing (QST) measures into the Phase II MAPP studies. Our group led the QST efforts in MAPP I, and for MAPP II have partnered with the UCLA site to implement an expanded QST testing protocol, including Conditioned Pain Modulation (CPM), and assessment of thresholds for other sensory experiences (visual, auditory). We hypothesize that QST will allow us to better separate endo-phenotypes (especially by identifying UCPPS participants with pan-sensory hyper-responsiveness that is clearly CNS in origin) as well as predict longitudinal course.
The University of Michigan MAPP discovery site was successful in providing scientific and organizational leadership and high recruitment and retention of research participants in Phase I. For Phase II we propose to do the same. In addition to being active participants in the Symptom Pattern Study that will serve as the main Phase II trans-MAPP study, we propose additional studies involving interventional phenotyping, genetics, and quantitative sensory testing that could also be incorporated into Phase II of the MAPP effort.
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