Uncovering the 'ORIGINS' of Diabetes

Type 2 Diabetes Clinical Trial

— ORIGINS  

Official title:

Uncovering the 'ORIGINS' of Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02226640
• Other study ID #: TRIMDFH 238153
• Status: Completed
• Phase: N/A
• First received: May 16, 2014
• Last updated: February 21, 2018
• Start date: November 2010
• Est. completion date: June 2014

Study information

• Verified date: February 2018
• Source: Translational Research Institute for Metabolism and Diabetes, Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a study to identify different subtypes of type 2 diabetes. The investigators will look for information at the molecular level, which may lead to personalized diagnosis and therapies.

Description:

Type 2 diabetes mellitus (T2DM) is approaching epidemic prevalence in the US adult population (over 1 in 10 of all US adults over 20). Diabetes is diagnosed based on fasting hyperglycemia, oral glucose intolerance or markers of hyperglycemia such as HbA1c. However, we now recognize that diabetes is a heterogeneous disorder. With the existing overly simplistic diagnostic criteria, treatment failure rates are high for virtually every agent currently in the drug arsenal - including insulin. In the late 1990's oncologists pioneered the use of high-throughput molecular technologies, such as transcriptome profiling and more recently metabolomics to identify discrete sub-classes of cancers that cannot be distinguished histologically or by a small number of biochemical markers. That effort rapidly accelerated the pace of scientific discovery and quickly led to the development of personalized cancer therapeutics. We believe that those cancer efforts provide a roadmap for biomarker discovery and personalized therapy in diabetes. molecular phenotyping (profiling the metabolome, transcriptome, and epigenome) with advanced bioinformatics analysis will identify discrete subtypes of diabetes - ushering in a new era of personalized diagnosis and therapy in diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18

• HbA1C < 8.0% *

• You have not gained or lost more than 3 kg or 6.6 pounds in the last 8 weeks

• You have not lost more than 10% of your heaviest body weight in your lifetime

• BMI < 25 kg/m2 or > 30 kg/m2

• Women: more than 1 year post-partum

• Have diabetes and are able to maintain accurate and reliable home glucose monitoring logs

Exclusion Criteria:

• Treatment with more than 2 of the following: metformin (Fortamet, Glucophage, Glumetza, Riomet), sulfonylureas (Glucotrol, Diabeta, Glynase, Micronase), Glucagon-like peptide-1 analogs (Byetta) and/or Dipeptidyl peptidase IV inhibitors (Januvia, Onglyza)

• Treatment with long acting Glucagon-like peptide-1 agonists within the last 3 months (i.e. exenatide once weekly)

• Treatment with thiazolidinediones (TZDs) (i.e. Avandia, Actos, Rezulin) within the last 3 months

• Known, untreated thyroid disease or abnormal thyroid function blood test.*

• Known diagnosis of liver disease (except NASH) or elevated liver function blood test

• Known diagnosis of kidney disease or elevated kidney function blood test

• Uncontrolled high blood pressure (BP > 140 systolic or > 90 diastolic)

• Start of or changes in oral contraceptives or hormone replacement therapy within the last 3 months

• Use of drugs or alcohol (> 3 drinks per day) within the last 5 years.

• Uncontrolled psychiatric disease that would interfere with study participation.

• History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable)

• History of organ transplant

• History of heart attack within the last 6 months

• Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for testing procedures

• Current anemia

• History of HIV, active Hepatitis B or C, or Tuberculosis

• Presence of clinically significant abnormalities on electrocardiogram.

• Current smokers (smoking any nicotine or non-nicotine product within the past 3 months)

• Use of any medications known to influence glucose, fat and/or energy metabolism within the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], etc.)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Type 2 Diabetes

Locations

Country	Name	City	State
United States	Translational Research Institute for Metabolism and Diabetes	Orlando	Florida

Sponsors (5)

Lead Sponsor	Collaborator
Translational Research Institute for Metabolism and Diabetes, Florida	Children's Hospital & Research Center Oakland, Duke Univeristy Sarah W. Stedman Nutrition & Metabolism Center, Florida Hospital, Sanford-Burnham Medical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (30)

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Cox J, Williams S, Grove K, Lane RH, Aagaard-Tillery KM. A maternal high-fat diet is accompanied by alterations in the fetal primate metabolome. Am J Obstet Gynecol. 2009 Sep;201(3):281.e1-9. doi: 10.1016/j.ajog.2009.06.041. — View Citation

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Mutch DM, Temanni MR, Henegar C, Combes F, Pelloux V, Holst C, Sørensen TI, Astrup A, Martinez JA, Saris WH, Viguerie N, Langin D, Zucker JD, Clément K. Adipose gene expression prior to weight loss can differentiate and weakly predict dietary responders. PLoS One. 2007 Dec 19;2(12):e1344. — View Citation

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Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, Goodpaster BH, Ruderman NB, Kelley DE. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab. 2010 Jan;298(1):E49-58. doi: 10.1152/ajpendo.00317.2009. Epub 2009 Nov 3. — View Citation

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Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. Erratum in: Nature. 2013 Jul 25;499(7459):504. — View Citation

Ukropcova B, McNeil M, Sereda O, de Jonge L, Xie H, Bray GA, Smith SR. Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor. J Clin Invest. 2005 Jul;115(7):1934-41. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perform 'deep' clinical and molecular phenotyping of 360 adults- Diabetic and Non-Diabetic	Phenotyping will include whole body composition (DEXA), substrate metabolism, classic diabetes phenotypes, and detailed molecular phenotyping of circulating mononuclear cells/ plasma, muscle and adipose tissue.	up to Day 9

External Links

•   Florida Hospital Translational Research Institute for Metabolism and Diabetes