Finding new-and-improved treatments

The primary focus of research has been regarding finding improved treatments for pediatric patients and finding ways to bring state of the art disease management and technology to pediatric patients.  The clinic has 2.4 FTE research staff to assist with current projects.

Current Studies

Diabetes Transformation study

Using new technology, a program will be developed to provide families in the future with more timely feedback on diabetes management, rather than just every 3 months in clinic. This study will also explore whether or not hemoglobin A1c levels can be improved by weekly review of blood glucose, insulin dosing, exercise, heart rate and sleep data which will be communicated to the clinic with a meter sync device, a FitBit ChargeHR wearable device and software. This study is funded through Children’s Foundation.

Development of Novel Pediatric Diabetes Education Materials for Somali Immigrants

A joint collaboration with the University of Minnesota aimed at developing and pilot testing an innovative, oral, video-based, patient-as-educator Type 1 Diabetes education program tailored to Somali immigrant families, taking into account such factors as parent literacy and numeracy level, culture, and religion. Somali parents and patients from both centers participated in workgroups along with Children’s and UMN endocrinologists, diabetes educators, dietitians, and a Somali coordinator to help determine areas of focus for the educational materials. In addition, we have been working with dietitians to develop visual carbohydrate counting materials (booklet with photos, video), specific for foods in the traditional Somali diet. The development of the video education program is ongoing, and the final phase of the study will involve piloting the video education program on a different group of Somali T1D patients and parents followed at UMN and Children’s, who have previously received standard ADA T1D education and to assess improvement in diabetes knowledge as measured before, immediately after, and 3 months after participating in the program.

Glucagon-Like Peptide-1 Agonist Effects on Energy Balance in Craniopharygioma with Hypothalamic Obesity (ECHO)

We have received funding for an NIH research project grant along with Seattle Children’s Hospital and Vanderbilt University Medical Center. The trial will examine the effect of GLP-1 agonist exenatide once weekly extended-release on clinical outcomes and metabolic parameters in a double-blind, placebo-controlled randomized trial with an open-label extension. Measures include body composition, free-living total daily energy expenditure by doubly labeled water, energy intake by 24hr dietary recall, activity by actimetry, as well as glucose tolerance and hormonal parameters of energy homeostatis and insulin resistance. The study will also test potential clinical, behavioral, metabolic, and neuroradiological predictors of treatment responses.

TrialNet-T1D Study

This multi-center study, sponsored by the University of South Florida’s TrialNet Coordinating Center, aims to improve the understanding of the natural history of T1D, as well as identifying and maintaining a pool of participants who may be eligible for entry into prevention trials, as these become available. To date, over 200 family members of T1D patients have been screened, and in September 2014, our first patient will complete oral glucose tolerance testing as part of the TrialNet Monitoring phase of the study. Additionally, Children’s was added as a site for the TrialNet Long-Term Follow-up (LIFT) study in late 2013. This study aims to follow TrialNet patients after a diagnosis of T1D.

Understanding the Etiology of Diabetes in Somali Children in the Twin Cities

This study in collaboration with the researchers at the University of Minnesota and Park Nicollet Health Care System will attempt to look at factors associated with the diagnosis of diabetes mellitus (both type 1 and type 2) in Somali children.  The incidence of these disorders is felt to be high in this ethnic group in individuals living in Minnesota and appears to be relatively uncommon in Somalia.

Liraglutide for T2D

This multi-center study, sponsored by NovoNordisk will be studying the use of Lirgalutide in combination with metformin in pediatric patients and the impact on their glycemic control. Liraglutide is a long acting GLP-1 receptor agonist with close similarity to native GLP-1 and may represent, in combination with metformin, a potential treatment alternative for the pediatric type 2 diabetes population. This trial will provide new data on the safety and efficacy of liraglutide in combination with metformin versus metformin in combination with placebo in treating children and adolescents with type 2 diabetes and may help to widen treatment options for the pediatric type 2 diabetes population.

Beloranib for Prader-Willi Syndrome

This Phase 3 clinical research study, sponsored by Zafgen, has completed its initial randomized, placebo-controlled testing of the effectiveness, tolerability, and safety of beloranib when given twice weekly to obese patients with Prader-Willi Syndrome (age 12-65) for 6 months.  The study also evaluated changes in quality of life and hunger and assessed responses in metabolic biomarkers and plasma exposure to beloranib in patients with Prader-Willi Syndrome. After the occurrence of two subject deaths in the study due to pulmonary emboli, the FDA placed a full clinical hold on the study until the preliminary data can be presented. The data have been released by Zafgen and look extremely promising, so we hope to receive a favorable review from the FDA to continue with the open-label portion of the study after implementing additional safety measures.

Collection of CYP21A2 Mutations for Laboratory Quality Assurance

In collaboration with the University of Minnesota and the Mayo Clinic, we are participating in a CDC quality assurance initiative for children who have been diagnosed with congenital adrenal hyperplasia (CAH).  One hundred-fifty families will participate in this study with 27 enrolled from Children’s. This pilot project will use blood specimens from patients with CAH and their parents for DNA mutation analysis, with the goal of developing quality assurance materials for early detection of CAH via molecular methods.

Accu-Chek Connect at School (CATS) Pediatric Study

This is an interventional study to learn more about the ACCU-CHEK® Connect Diabetes Management System (DMS) and its features. The main purpose of this study is to see if the ACCU-CHEK® Connect DMS can help reduce diabetes-related distress among parents/caregivers of school-age children (age 6-18 years) with T1DM on MDI therapy. This study will compare the effects of the ACCU-CHEK® Connect DMS with the effects of usual care using a standard blood sugar monitoring device.

Phase IV Endocrine Trials

The Endocrine clinic also participates in a phase IV clinical trial assimilating clinical outcome data for patients taking growth hormone and previously participated in trials assimilating clinical outcome data for patients taking insulin like growth factor.  Because growth hormone deficiency and insulin like growth factor deficiency are fairly rare disorders, accumulation of adequate outcome and safety data is unrealistic for any single clinic.  Pharmaceutical companies manufacturing growth hormone have had phase IV studies ongoing since the introduction of synthetic growth hormone in 1985.  These have accumulated more than 100,000 patient years of data.  The clinic has participated in three of these studies with only one ongoing at present.  Approximately 150 patients are enrolled, with new patients approached and consented each week.

Novel Long-Acting Recombinant Human Growth Hormone (VRS-317) in Children with Growth Hormone Deficiency

We are actively recruiting for a Phase 3 trial studying VRS-317 in children with growth hormone deficiency. VRS-317 is a novel, long-acting human growth hormone (hGH). This fusion protein consists of recombinant human growth hormone (rhGH) and the all-natural hydrophilic amino acids referred to a XTEN. This product has been designed to provide improved therapeutic outcomes for patients with GHD, including better compliance/convenience, fewer side effects, as well as enhanced administration of a liquid formulation via a fine-gauge needle.

A Phase IV, Multicenter, Open-Label Study of the Immunogenicity of Nutropin AQ® V1.1 [Somatropin (rDNA Origin) Injection] Administered Daily to Naïve Growth Hormone-Deficient Children

We are working with Genentech on a phase 4 trial studying the immunogenicity of Nutropin AQ®. To use the most advanced methodology and equipment to ensure a continued supply of Nutropin AQ, Genentech has updated its manufacturing process. Chemical and biological characterization (including potency) has demonstrated comparability of drug substance produced by the original and updated manufacturing processes and, based on this, the new manufacturing process that is used to produce Nutropin AQ v1.1 has been approved by FDA. This open-label study, performed in children with GHD, will assess the immunogenicity profile of Nutropin AQ produced by the new manufacturing process.

Multi-Center, Prospective, Observational Study of the TS (Threshold Suspend) Feature with a Sensor-Augmented Pump System in Pediatric Patients with Type 1 Diabetes

This longitudinal, multi-center trial sponsored by Medtronic aims to observe the Threshold Suspend (TS) feature with a sensor-augmented insulin pump in patients 2–15 years with Type 1 diabetes. The study will measure the change in A1C from baseline over a period of one year while subjects are wearing the study pump. The objective is to demonstrate that home use of Threshold Suspend (TS) is not associated with glycemic deterioration in pediatric patients with type 1 diabetes, as measured by change in A1C.

Publications and Presentations

Posters

Kelly AS, Metzig AM, Rudser KD, Fitch AK, Fox CK, Nathan BM, Steinberger J, Deering M, Schwartz BL, Abuzzahab MJ, Gandrud LM, Moran A, Billington CJ, Schwarzenberg SJ. Exenatide as a Weight-Loss Therapy in Extremely Obese Youth without Diabetes. American Diabetes Association Meeting. 2011.

Sarafoglou K, Miller BS, Turcotte L, Wickremasinghe A, Pittock S, Kyllo J, Otten N, Addo Y, Himes JH. The Impact of Hydrocortisone Dosage on Body Mass Index in CAH – The Minnesota Cohort. Poster presentation. Pediatric Academic Society Annual Meeting. 2012.

Kelly AS, Rudser KD, Nathan BM, Fox CK, Metzig AM, Coombes BJ, Fitch AK, Bomberg EM, Abuzzahab MJ. The Effect of Glucagon Like Peptide-1 Receptor Agonist Therapy on Body Mass Index in Adolescents with Severe Obesity. The Obesity Society Annual Meeting. 2012.

Jimenez-Vega JM, Kamrath H, Gandrud L, Hennum J. Risk of Over the Counter Vitamin D Supplements: A case of unintentional chronic vitamin D intoxication of an infant. 9th Joint Meeting of Paedriatic Endochrinology. 2013.

Cohen P, Counts D, Abuzzahab MJ, Gut R, Germak J. Responses to Growth Hormone Treatment in Pediatric Patients with Prader-Willi Syndrome: Analysis of 3-Year Data from the ANSWER Program®. Pediatric Academic Society Annual Meeting. 2012.

Cohen P, Counts D, Abuzzahab MJ, Gut R, Germak J. Responses to Growth Hormone Treatment in Pediatric Patients with Prader-Willi Syndrome: Analysis of 3-Year Data from the ANSWER Program®. GRS and IGF Society International Congress. 2012.

Oral Presentations

Sarafoglou K, Miller BS, Turcotte L, Wickremasinghe A, Pittock S, Kyllo J, Otten N, Addo Y, Himes JH. The Impact of Hydrocortisone Dosage on Final Adult Height in Congenital Adrenal Hyperplasia – the Minnesota cohort. Platform session. Pediatric Academic Society Annual Meeting. 2011.

Abuzzahab MJ. Exenatide in Extreme Pediatric Obesity. University of Minnesota Clinical and Translational Study Institute Meeting. 2011.

Abuzzahab MJ, Daniels M, Kelly AS, Miller B, Kyllo J.  Effects of Exenatide on Hypothalamic Obesity.  Platform session. Pediatric Academic Society Annual Meeting. 2012.

Abuzzahab MJ. Effects of Exenatide on Hypothalamic Obesity. Children’s Pediatric Research Conference. 2013.

Abuzzahab MJ. Exenatide in Extreme Pediatric Obesity. International Congress of Endocrinology and the Endocrinology Society. 2014.

Articles

Kelly AS, Metzig AM, Rudser KD, Fitch AK, Fox CK, Nathan BM, Deering M, Schwartz BL, Abuzzahab MJ, Gandrud LM, Moran A, Billington CJ, Schwarzenberg SJ.  Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study.  Obesity 2012;20(2):364-370.

Kelly AS, Rudser KD, Nathan BM, Fox CK, Metzig AM, Coombes BJ, Fitch AK, Bomberg EM, Abuzzahab MJ. The Effect of Glucagon-Like Peptide-1 Receptor Agonist Therapy on Body Mass Index in Adolescents with Severe Obesity: A Randomized, Placebo-Controlled, Clinical Trial. JAMA Pediatr. 2013 Apr;167(4):355-60.

Sarafoglou K, Banks K, Kyllo J, Pittock S, Thomas W. Cases of Congenital Adrenal Hyperplasia Missed by Newborn Screening in Minnesota. JAMA. 2012 Jun 13;307(22):2371-4.

Bostrom B, Uppal P, Chu J, Messinger Y, Gandrud L, McEvoy R. Safety and efficacy of metformin for therapy-induced hyperglycemia in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2013 Oct;35(7):504-8.

Sarafoglou K, Addo OY, Turcotte L, Otten N, Wickremasinghe A, Pittock S, Kyllo J, Lteif AN, Himes JH, Miller BS. Impact of hydrocortisone on adult height in congenital adrenal hyperplasia-the Minnesota cohort. J Pediatr. 2014 May;164(5):1141-1146.e1.

Melachuri S, Gandrud L, Bostrom B. The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2014 Jun;61(6):1003-6.

Griffin KJ, Thompson PA, Gottschalk M, Kyllo JH, Rabinovitch A. Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2014 Sep;2(9):710-8.

Bomberg EM, Addo OY, Kyllo J, Gonzalez-Bolanos MT, Ltief AM, Pittock S, Himes JH, Miller BS, Sarafoglou K. The relation of peripubertal and pubertal growth to final adult height in children with classic congenital adrenal hyperplasia. J Pediatr. (In Press).

Other publications

Bode B, Kyllo J, Kauffmann F. Pediatric Pumping Protocol, A guide to Insulin therapy initiation. Medtronic Medical Education Publications. 2012.

We are also in the process of reviewing data and developing manuscripts for the following studies:

  • IGF Generation Tests
  • Effects of Exenatide on Hypothalamic Obesity
  • A Retrospective Study on Predictors of HbA1C in Children with Type I Diabetes Mellitus on Continuous Glucose Monitoring System
  • A Retrospective Study on HbA1C Levels in Children and Adolescents with Type 1 Diabetes Mellitus Using the iPro CGMS

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