Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment | RxWiki

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

Overview[ - collapse ][ - ]

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	Ketosis Prone Diabetes Diabetes Ketoacidosis Hyperglycemia
Intervention	Drug: metformin Drug: placebo Drug: Sitagliptin
Phase	Phase 4
Sponsor	Dawn Smiley MD
Responsible Party	Emory University
ClinicalTrials.gov Identifier	NCT01099618
First Received	March 15, 2010
Last Updated	November 20, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	March 15, 2010
Last Updated Date	November 20, 2013
Start Date	March 2010
Estimated Primary Completion Date	February 2014
Current 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)
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin 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
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition	Ketosis Prone Diabetes Diabetes Ketoacidosis Hyperglycemia
Intervention	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 Names: GlucophageDrug: 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. 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 Names: Januvia
Study Arm (s)	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). 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). 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).

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	48
Estimated Completion Date	February 2014
Estimated Primary Completion Date	January 2014
Eligibility Criteria	Inclusion Criteria: 1. 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). 2. 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: 1. significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes; 2. recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism; 3. bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies; 4. pregnancy, 5. have an allergy to any component of metformin or sitagliptin.
Gender	Both
Ages	19 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Contact: Dawn D Smiley, MD 404-778-1674 dsmiley@emory.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01099618
Other Study ID Numbers	IRB00026272
Has Data Monitoring Committee	Yes
Information Provided By	Emory University
Study Sponsor	Dawn Smiley MD
Collaborators	Not Provided
Investigators	Principal Investigator: Dawn D. Smiley, MD Emory School of Medicine
Verification Date	November 2013

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