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Nep hrotic Syndrome S tu dy Ne twork

Patients as Clinical Trial Partners Deb Gipson, MS, MD Associate Professor of Pediatrics Office of Research, University of Michigan. Nep hrotic Syndrome S tu dy Ne twork. Defining New Pathways and Targets. 1712 Patients in Patient Contact Registry. Framework. Steps in Clinical Trials.

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Nep hrotic Syndrome S tu dy Ne twork

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  1. Patients as Clinical Trial Partners Deb Gipson, MS, MD Associate Professor of Pediatrics Office of Research, University of Michigan Nephrotic Syndrome Study Network Defining New Pathways and Targets 1712 Patients in Patient Contact Registry

  2. Framework

  3. Steps in Clinical Trials

  4. Example: Patient Questions Patient query 0: Now that I have this disease, what will happen to me? (outcome) Patient query 1: What is the right choice of treatment for this disease? (standard therapy) Patient query 2: Reviewing the possible side effects of the typical treatment for this disease, what are my other options? (Risk/Benefit) Patient query 3: Treatment 1 did not work. What are my options now? (Treatment resistance)

  5. Quick Introduction to Nephrotic Syndrome (NS) • Kidney Disease that affects people of all ages • Abnormally high levels of protein loss in urine • May cause loss of kidney function • To the patient: • Swelling • Fatigue • High Blood Pressure • Kidney Failure

  6. Disease Course in NS +20% SRNS 26% FRNS 60% Proteinuria 14% Time (weeks)

  7. Treatment Resistance and Kidney Survival with NS (FSGS) b. Adults a. Children CR 12 12 8 5 5 PR 20 18 13 11 9 NR 28 25 20 10 9 Gipson, Jennette, Massengill, et al, PedsNeph, 2006 Troyanov, et al, JASN, 2005

  8. Funding • Patients and Patient Advocacy Lobby for Research • Congress directs NIH to address unmet need of treatments for FSGS

  9. Patients and Clinicians inform Question Compare standard therapy to alternate therapy to determine which therapy: 1. Best control of disease on treatment? Urine protein with preserved kidney function 2. Maintain control of disease off treatment? Urine protein with preserved kidney function 3. Least Side Effects? • Kidney function • Others

  10. FSGS RCT: MMF+Dexa vs CSA Clinicians Inform Design Week Randomize All:Pred +ACEi 0 26 52 78 CSA MMF + Dex Primary Outcome 6 months ACEi Secondary Outcome Gipson, KI, 2011

  11. Patients and Clinicians Inform Design FSGS CT: MMF+DEX vs CSA • Outcome • Primary: proteinuria reduction • Secondary: Relapse after stopping test therapy • Secondary: Side Effects • Power • N=138; 80% power to detect 18% difference in response Inclusion • Age 2 – 40 years • eGFR ≥ 40 ml/min/1.73m2 • Up/c > 1.0 g/g • Steroid resistance • Biopsy confirmed FSGS • Exclusion: Pause for Safety • Prior CNI or MMF • Transplant • Malignancy • Diabetes mellitus Gipson D, KI, 2011

  12. FSGS CT Results Patients and Researchers: Interpretation of results Conclusion 1: Neither study treatment is superior for FSGS Conclusion 2: Response to either treatment is not acceptable NR Figure: 6 Ordinal Outcome PR CR CR 9 vs 19 % PR 24 vs 26 % NR 67 vs 54 % Gipson et al, 2011

  13. Patients • We need options when standard therapies fail • We need options to include older adults as well as children and young adults • We need faster results Researchers • We need better outreach to patients for enrollment

  14. Bodyimageconnection.com

  15. FONT Study Networkfor Patients with Treatment Resistant FSGS Sponsor: NIH/NIDDK

  16. Patient Participant on Outreach CommitteeWebsite and Eligibility Screener FontTrial.org

  17. Patient Participant on Outreach CommitteeWebsite and Eligibility Screener

  18. FONT II Design: Ranking and Selection TrialAdaptive Trial Design **Maximize Results and Minimize Patient Number** Eligible Patients with Resistant FSGS RANDOMIZATION Adalimumab N=17 Standard Rx N=17 Galactose N=17 Pause for Efficacy Review ≥2/17 with Up/c<50% baseline and stable GFRe YES, continue recruitment to N=42* NO, discontinue study arm Sponsor: NIH/NIDDK Trachtman, Gipson et al, 2011

  19. Evidence to Practice Imperfect Impact Dissemination Implementation Important Question Trial Design Sample Size Patient Community Engaged Clinical Community Engaged Sponsor (Funding) Engaged

  20. Development of a Decision Support Tool for Nephrotic Syndrome Management Meg Modes – Patient Advocate Marilyn Hailperin – NephCure Foundation Deb Gipson, Larry An, Patrick Nachman, Michelle Hladunewich, Heather Beanlands, Emily Herreshoff

  21. Specific Aims • Identify the types of health related decisions and the factors that influence health related decision making among patients and parents with nephrotic syndrome. • Identify the physician perspective of nephrotic syndrome, treatment options and factors that influence disease management. • Develop and test a patient-centered decision support tool that will facilitate shared learning by the patient and healthcare team as part of chronic disease management.

  22. Data Collection Focus Groups (F) and Individual Interviews (I) Data Interpretation Results Prioritization

  23. Patient Map Overview and Content

  24. Individual Tree

  25. Physician View: Patient Overview

  26. Physician View: Review Questions

  27. Shared Learning Tool Cycle 2: Clinical Trial

  28. Lessons Learned • Patients can and want to be involved in the study pipeline • Patients and Researchers • Often speak different languages • May need translators/facilitators until they learn to speak a common language • Both researchers and patients • Get better with practice • Need advice • May benefit from mentorship

  29. Questions?

  30. FSGS CT Results FSGS CT: MMF+DEX vs CSA Gipson et al, 2011

  31. As kidney scarring is part of the pathway to kidney failure, can we disrupt scarring? Wada, KI 2007

  32. Galactose Negates Permeability Factor Potential Mechanisms of Action FSPF • Permeability factor may gain access to podocyte by sugar binding. • Galactose may block the binding between factor and podocyte. • Factor-galactose complex may be removed by specific receptors in liver or other tissues. Filtration slits Podocytes galactose galactose galactose FSPF FSPF galactose galactose FSPF FSPF-galactose complex FSPF-galactose complex Galactose receptors Savin VJ, et al., 2008

  33. “My Readings”

  34. Treatment Response is Improved with Proper Drug Dosing p<0.05 0 100 200 300 0 100 200 300 Time to Relapse (days) GellermannJ, JASN 2013

  35. FONT Study Networkfor Patients with Treatment Resistant FSGS Adalimumab (TNF-α-MAB) Rosiglitazone (PPAR- ) Galactose TGF- β -MAB Rosiglitazone Adalimumab (TNF-α-MAB) Galactose TGF-β-MAB Sponsor: NIH/NIDDK

  36. Novel Agent Selection • Biologic Plausibility • Preclinical data • Clinical data • Safety profile • Is there an option beyond the typical immune system target?

  37. Tree Groves

  38. Drug Dosing and Nephrotic Syndrome • Significant proteinuria • Alters medication clearance Adalimumab r2= 0.9, p=0.001 Joy, Gipson, Trachtman, 2008

  39. Drug Dosing in Nephrotic Syndrome http://2012.igem.org/Team:Penn

  40. iNSider Clinical Trial Proposed Evaluate the impact of • iNSider shared learning tool + standard education • Standard education alone

  41. Patients as Clinical Trial Partners Deb Gipson, MS, MD Associate Professor of Pediatrics Director, Honest Broker Office University of Michigan

  42. Shared Learning Decision Support Tool iNSider

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