Document text
Principal Investigator: Gary Fanger
Organization: RISE THERAPEUTICS, LLC
Fiscal Year: 2024
Award: $995,869
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Project Summary
Type 1 diabetes (T1D) is a devastating disease and there is no current curative treatment, with insulin being
the only product available. T1D affects not only glycemic control but also many important aspects of a patient's
life, including emotional well-being, quality of life, working ability, and social interactions29. In addition, persons
with T1D present increased risk of developing other serious complications. Therefore, there is an urgent need
to develop new cutting-edge strategies for T1D management.
The steep rise in the incidence and prevalence of T1D cannot be explained solely by genetic factors
implicating the environment, and specifically the gut microbiome, as a culprit for the disease
etiopathogenesis45. The gut microbiome influences multiple host functions, including immunity, and persons
with T1D present changes in gut microbiota associated with immunological deregulation and gut leakiness6.
Clinical studies demonstrate that fecal microbiome therapy (FMT) and probiotics can halt the progression of
new onset T1D13, corroborating the importance of the gut microbiome.
A promising and safe approach for the treatment of T1D that leverages the body’s own natural microbiome-
associated immune regulatory mechanisms is the use of resistant starches. High amylose starch (HAMS) is a
well-tolerated source of dietary fiber that modulate the gut microbiome and the host immune response. HAMS
consumption shifts the gut microbiome profile towards dietary fiber fermenters, producing the beneficial short
chain fatty acids SCFAs. However, HAMS only partially ameliorates T1D in humans. A potentially better
strategy is to use HAMS that has been esterified, releasing larger amounts of SCFAs in the intestinal tract and
eventually the circulation. Rise Therapeutics is developing R-5280, a modified version of HAMS that has been
butyrylated and acetylated. In our prior Phase 1 clinical trial enrolling adolescents with recent onset of T1D,
oral administration of R-5280 increased SCFA production leading to improved overall glycemic control. In
addition, R-5280 consumption resulted in significant increases in specific beneficial metabolites, and reduction
of inflammatory T cells. Given the limited success of prior therapeutic strategies and potential long-term risks of
immunomodulatory therapies in patients with T1D, the use of a microbiome modulating therapy like R-5280
offers a simple, safe, and inexpensive alternative approach to mitigating this devastating disease.
The goal of this proposal is to perform a confirmatory double blinded placebo-controlled Phase 2 clinical trial of
adolescents with early onset of T1D. The key aims of this proposal are: 1) compounding of R-5280 and
placebo to prepare for patient distribution; 2) execute the Phase 2 clinical trial; and 3) expand biomarker
discovery and characterization. Successful commercialization of R-5280 will provide a profound medical
advancement for treating T1D.
Terms: <16 year old><16 years of age><Acetylation><Adolescent><Adolescent Youth><Affect><Age><American><Amylose><Attention><Autoimmune Diseases><BMI><BMI percentile><BMI z-score><Beta Cell><Biological Agent><Biological Markers><Biological Products><Biological Response Modifier Therapy><Biological Therapy><Blinded><Body mass index><Brittle Diabetes Mellitus><Chronic><Circulation><Clinical><Clinical Research><Clinical Study><Consumption><Continuous Glucose Monitor><Diabetes Mellitus><Diagnosis><Dietary Fiber><Disease><Disorder><Double-Blind Method><Double-Blind Study><Double-Blinded><Double-Masked Method><Double-Masked Study><Drug usage><Drugs><Early-Stage Clinical Trials><Emotional well being><Enrollment><Environment><Esterification><Feces><Feels well><Fermentation><GI microbiome><GI microbiota><Gastrointestinal microbiota><Genetic><Goals><Health><Human><Human Resources><Humulin R><IDDM><Immune><Immune Modulation Therapy><Immune response><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunologic Subtyping><Immunological><Immunological response><Immunologically><Immunologics><Immunophenotyping><Incidence><Indiana><Inflammatory><Injectable><Insulin><Insulin Cell><Insulin Secreting Cell><Insulin-Dependent Diabetes Mellitus><Intestinal><Intestinal Leakage><Intestines><Juvenile-Onset Diabetes Mellitus><Ketosis-Prone Diabetes Mellitus><Label><Leaky Gut><Life><Long-Term Effects><Longterm Effects><Manpower><Mediating><Medical><Medication><Modern Man><Normal mental condition><Normal mental state><Normal psyche><Novolin R><Oral><Oral Administration><Oral Drug Administration><Pancreatic beta Cell><Pancreatic β-Cell><Patients><Persons><Pharmaceutical Preparations><Pharmacies><Pharmacodynamics><Pharmacy facility><Phase 1 Clinical Trials><Phase 2 Clinical Trials><Phase I Clinical Trials><Phase I Study><Phase II Clinical Trials><Placebo Control><Placebos><Prevalence><Probiotics><Process><Production><Property><Protocol><Protocols documentation><Psychological Well Being><QOL><Quality of life><Quetelet index><Randomized><Regular Insulin><Research Specimen><Residual><Residual state><Resistance><Risk><Safety><Sense of well-being><Severities><Sham Treatment><Short-Chain Fatty Acids><Social Interaction><Source><Specific qualifier value><Specified><Specimen><Starch><Structure of beta Cell of islet><Sudden-Onset Diabetes Mellitus><T-Cells><T-Lymphocyte><T1 DM><T1 diabetes><T1D><T1DM><Testing><Therapeutic><Time><Training><Treatment Period><Type 1 Diabetes Mellitus><Type 1 diabetes><Type I Diabetes Mellitus><Universities><Volatile Fatty Acids><Well in self><age 16 years><ages><autoimmune condition><autoimmune disorder><autoimmunity disease><autoreactive T cell><bio-markers><biologic marker><biological therapeutic><biological treatment><biologically based therapeutics><biologics><biomarker><biomarker discovery><biopharmaceutical><biotherapeutic agent><biotherapeutics><biotherapy><bowel><clinical trial enrollment><commercialization><continuous blood glucose monitor><continuous blood sugar monitor><continuous glucose measurement><continuous sugar monitor><cost><curative intervention><curative therapeutic><curative therapy><curative treatments><diabetes><diabetes management><diabetes mellitus management><diabetic management><dietary><digestive tract microbiome><drug use><drug/agent><early onset><emotional wellbeing><emotional wellness><enroll><enteric microbial community><enteric microbiome><enteric microbiota><fecal microbiome><gastrointestinal microbial flora><gastrointestinal microbiome><glycemic control><gut commensal><gut community><gut flora><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiome><gut microbiota><gut microbiotic><gut microflora><gut-associated microbiome><host response><immune modulating therapies><immune modulatory therapies><immune system response><immune-modulation treatment><immunomodulation therapy><immunomodulation treatment><immunomodulator therapies><immunomodulator treatment><immunomodulator-based therapies><immunomodulatory therapies><immunomodulatory therapy><immunomodulatory treatment><immunophenotype><immunoresponse><improved><insulin dependent diabetes><insulin dependent diabetes mellitus onset><insulin dependent type 1><insulin secretion><insulin sensitivity><intestinal biome><intestinal flora><intestinal microbiome><intestinal microbiota><intestinal microflora><intestinal tract microflora><intraoral drug delivery><islet><juvenile><juvenile diabetes><juvenile diabetes mellitus><juvenile human><ketosis prone diabetes><manufacture><mental well-being><mental wellbeing><mental wellness><metabolism measurement><metabolome><metabolomics><metabonome><metabonomics><microbiome><microbiome intervention><microbiome therapeutics><microbiome therapy><microbiome treatment><microbiome-based intervention><microbiome-based therapeutic><microbiome-based therapy><microbiome-based treatment><new approaches><novel><novel approaches><novel strategies><novel strategy><pancreas beta cell><pancreas β cell><pancreatic b-cell><participant enrollment><patient enrollment><patient population><personnel><phase 1 study><phase 1 trial><phase 2 trial><phase I protocol><phase I trial><phase II protocol><phase II trial><placebo controlled><psychological wellbeing><psychological wellness><randomisation><randomization><randomized placebo control trial><randomized placebo controlled trial><randomly assigned><resistant><response biomarker><response markers><self wellness><self-reactive T cell><sense of wellbeing><sex><sham therapy><side effect><sixteen year old><sixteen years of age><stem><stool><stool microbiome><stool-associated microbiome><success><thymus derived lymphocyte><treatment days><treatment duration><type 1 diabetes onset><type I diabetes><type one diabetes><whole grain><β-cell><β-cells><βCell>