Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment - Full Text View

Purpose

We will plan to study 48 subjects with diabetes and 8 patients without diabetes. The blood tests from the subjects without diabetes will be helpful in assessing the "normal" response compared to subjects with diabetes. Diabetic subjects that no longer need insulin will be randomly placed (like the flip of a coin) on a diabetes pill called metformin, a diabetes pill called sitagliptin or a placebo pill (a pill without active medication). Subjects on pills will be followed for 3½ years and undergo blood tests at specified intervals to assess their ability to make insulin. These studies will allow a better understanding of the factors that lead to high blood sugar in patients with KPDM and direct the best diabetes treatment for this patient population.

Hypothesis: Metformin therapy or sitagliptin therapy compared to placebo, will improve β-cell function, insulin sensitivity, and allow for a longer period of time prior to encountering an insulin-deficient relapse after discontinuation of insulin therapy.

Condition	Intervention	Phase
Diabetes Mellitus, Insulin-Dependent Diabetes Ketoacidosis Hyperglycemia	Drug: metformin Drug: placebo Drug: Sitagliptin	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Ketosis-Prone Diabetes in African Americans: Predictive Markers, Underlying Mechanisms, and Treatment Outcomes: The Effects of Metformin vs. Sitagliptin on Beta-Cell Preservation in Obese Subjects With Ketosis-Prone Type 2 Diabetes Mellitus

Resource links provided by NLM:

Genetics Home Reference related topics: type 1 diabetes

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 1 Diabetes Type 2 Hyperglycemia Obesity

Drug Information available for: Metformin Metformin hydrochloride Sitagliptin Sitagliptin phosphate

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Predictive of short- and long-term near-normoglycemic remission [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Determine what clinical, metabolic and immunogentic markers, alone or in combination, are predictive of short- and long-term near-normoglycemic remission. Clinical features (weight, BMI, age in years, sex, FHx of diabetes), metabolic (bicarbonate, ph, glucose level, BOHB level), immunogenetic markers (GAD, ICA)

Secondary Outcome Measures:

Molecular markers in skeletal muscle [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Correlate specific molecular markers in skeletal muscle with patient outcome, β-cell function, and insulin sensitivity. Western blots will be performed on the muscle samples. OGTT will be done to follow beta-cell function and a frequently sampled IVGTT will be done to assess insulin sensitivity
Length of time in remission [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Those patients that are able to discontinue insulin therapy at or <12 weeks will be randomized to 1 of 3 study arms. They will be followed for the duration of the study.

Estimated Enrollment:	48
Study Start Date:	March 2010
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Metformin All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg (n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: metformin The study subject will receive metformin (MET) 1000 mg tablet once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period. Other Name: Glucophage
Active Comparator: Sitagliptin All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000 mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg (n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: Sitagliptin The study subject will receive a sitagliptin 100mg once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period. Other Name: Januvia
Placebo Comparator: Placebo All newly diagnosed subjects with KPDM that are able to discontinue insulin after 12 weeks or less will be randomized in double-blind fashion to receive either metformin 1000 mg, sitagliptin 100mg or placebo once daily. Subjects that do not achieve remission will continue to receive insulin therapy and will discontinue the protocol. A total of 48 obese subjects with DKA (N=24) and obese subjects with hyperglycemia without ketoacidosis (n=24) will be equally randomized to receive metformin (MET) 1000 mg(n=16), sitagliptin (SIT) 100mg (n=16) or placebo (n=16).	Drug: placebo The study subject will receive a placebo tablet once a day as long as the patient maintains near-normoglycemic remission (BG < 130mg/dL and A1c <7%) during the 3-year follow-up period.

Eligibility

Ages Eligible for Study:	19 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

All newly diagnosed overweight/obese (BMI >/=28 kg/m2) African-American patients with new-onset DKA and/or severe hyperglycemia and without apparent precipitating cause will be considered for inclusion into the study. The diagnosis of DKA will be established by standard criteria (blood glucose > 250 mg/dL, pH < 7.3, HCO3 < 18 mmol/L, increased anion gap).
The hyperglycemic group will include patients with an admission plasma glucose > 400 mg/dL but without the presence of metabolic acidosis or ketosis.

Exclusion Criteria:

significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes;
recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism;
bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies;
pregnancy,
have an allergy to any component of metformin or sitagliptin.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01099618

Contacts

Contact: Dawn D Smiley, MD	404-778-1674	dsmiley@emory.edu
Contact: Guillermo Umpierrez, MD	404-778-1663	geumpie@emory.edu

Locations

United States, Georgia
Grady Memorial Hospital	Recruiting
Atlanta, Georgia, United States, 30303
Contact: Dawn D Smiley, MD 404-778-1664 dsmiley@emory.edu
Contact: Guillermo Umpierrez, MD 4047781663
Principal Investigator: Dawn Smiley, MD, MSCR

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator:

Dawn D. Smiley, MD

Emory School of Medicine

More Information

No publications provided

Responsible Party:	Dawn Smiley, MD, Emory University School of Medicine
ClinicalTrials.gov Identifier:	NCT01099618 History of Changes
Other Study ID Numbers:	26272
Study First Received:	March 15, 2010
Last Updated:	March 7, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Hyperglycemia
Ketosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Acidosis

Acid-Base Imbalance
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013