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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dawn Smiley MD, Emory University
ClinicalTrials.gov Identifier:
NCT01099618
First received: March 15, 2010
Last updated: May 24, 2014
Last verified: May 2014
  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
Ketosis Prone Diabetes
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:


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: August 2014
Primary Completion Date: February 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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Dawn Smiley MD
Investigators
Principal Investigator: Dawn D. Smiley, MD Emory School of Medicine
  More Information

No publications provided

Responsible Party: Dawn Smiley MD, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01099618     History of Changes
Other Study ID Numbers: IRB00026272
Study First Received: March 15, 2010
Last Updated: May 24, 2014
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 July 22, 2014