Ketosis Prone DiabetesPhase 4NCT01099618
Ketosis-Prone Diabetes Mellitus (KPDM): Metformin Versus Sitagliptin Treatment
A Phase 4 study testing metformin and Sitagliptin in people with Ketosis Prone Diabetes and Diabetes Ketoacidosis, run by Dawn Smiley MD at 1 site in United States.
Trial summary
The study intends on enrolling 48 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). Read more about this study
- Who is it for?
- Ages 19 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Ketosis Prone Diabetes, Diabetes Ketoacidosis, Hyperglycemia
- What is being tested?
- metformin and Sitagliptin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Aug 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
The study intends on enrolling 48 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 ketosis-prone diabetes mellitus (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.
- Conditions
- Ketosis Prone Diabetes, Diabetes Ketoacidosis, Hyperglycemia
- Being tested
- metformin, placebo, Sitagliptin
- Medical subject headings
- Diabetes Mellitus, Type 1, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metforminDrug
Also called Glucophage
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.
placeboDrug
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.
SitagliptinDrug
Also called Januvia
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | 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). Receives: Drug: metformin |
| Sitagliptin | Active comparator | 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). Receives: Drug: Sitagliptin |
| Placebo | Placebo comparator | 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). Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of Remission
For those patients that are able to discontinue insulin therapy at or <12 weeks, how long were they able to well controlled with an A1c <7% on the agent that they were randomized to.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2010 (estimated)
- Study startMar 2010
- Primary completionFeb 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ketosis Prone DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dawn Smiley MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dawn Smiley MD, Emory University
- Investigators
- Dawn D. Smiley, MD, Principal investigator, Emory School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01099618
- Sponsor's protocol ID
- IRB00026272
- Status last verified
- May 2014
- First submitted
- 15 Mar 2010
- Last updated
- 18 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Vellanki P, Stefanovski D, Anzola II, Smiley DD, Peng L, Umpierrez GE. Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises. BMJ Open Diabetes Res Care. 2020 May;8(1):e001062. doi: 10.1136/bmjdrc-2019-001062.
PubMed 32475838Vellanki P, Smiley DD, Stefanovski D, Anzola I, Duan W, Hudson M, Peng L, Pasquel FJ, Umpierrez GE. Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises. Diabetes Care. 2016 Nov;39(11):1948-1955. doi: 10.2337/dc16-0406. Epub 2016 Aug 29.
PubMed 27573938
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01099618
- Acronym / sponsor ID
- IRB00026272
- Conditions
- Ketosis Prone Diabetes, Diabetes Ketoacidosis, Hyperglycemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Dawn Smiley MDUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 7 Apr 2010 (estimated)
- Results
- Posted 18 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study intends on enrolling 48 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 ketosis-prone diabetes mellitus (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: metforminAll 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). |
| Sitagliptin | Active comparator | Drug: SitagliptinAll 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 | Placebo comparator | Drug: placeboAll 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). |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metforminAlso: GlucophageThe 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. | Drug | Metformin |
| placeboThe 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 | Placebo |
| SitagliptinAlso: JanuviaThe 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. | Drug | Sitagliptin |
Primary outcome
Length of Remission
Time frame: 3 years
For those patients that are able to discontinue insulin therapy at or <12 weeks, how long were they able to well controlled with an A1c <7% on the agent that they were randomized to.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32475838Vellanki P, Stefanovski D, Anzola II, Smiley DD, Peng L, Umpierrez GE. Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises. BMJ Open Diabetes Res Care. 2020 May;8(1):e001062. doi: 10.1136/bmjdrc-2019-001062.
- Derived from this study: PubMed 27573938Vellanki P, Smiley DD, Stefanovski D, Anzola I, Duan W, Hudson M, Peng L, Pasquel FJ, Umpierrez GE. Randomized Controlled Study of Metformin and Sitagliptin on Long-term Normoglycemia Remission in African American Patients With Hyperglycemic Crises. Diabetes Care. 2016 Nov;39(11):1948-1955. doi: 10.2337/dc16-0406. Epub 2016 Aug 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dawn D. Smiley, MD principal investigator
Emory School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing metformin and Sitagliptin in people with Ketosis Prone Diabetes and Diabetes Ketoacidosis, run by Dawn Smiley MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of Remission (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01099618, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2015.