Function of Metformin at the Cellular Level and Best Dosing for Children and Adults With DM or Pre-DM
The investigators know that metformin works at the level of the cells in the body by acting on a protein called CREB binding protein or CBP. What the investigators do not know is how this process is affected when the dose of the metformin is increased or changed.
Currently the same doses of metformin are often used in both children and adults, but it is possible that the dose of metformin should be based on age and weight. Understanding how CBP works could potentially help us to tailor metformin treatment individually for patients based on their age, weight and CBP response.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Pilot Study of Metformin-induced CBP Phosphorylation at the Cellular Level and Corresponding Clinical Dose Response in Adults and Children|
- CBP Phosphorylation [ Time Frame: Approximately Week 10 ] [ Designated as safety issue: No ]To assess metformin-induced CBP phosphorylation in circulating white blood cells both in vivo and ex vivo and determine its relationship to subsequent changes in body mass index, fasting blood glucose, insulin and glucagon.
- Effect of dose escalation [ Time Frame: Approximately Week 10 ] [ Designated as safety issue: No ]Compare the effect of dose escalation of metformin on CBP phosphorylation in white blood cells in both in vivo and ex vivo assays to subsequent physiological changes in vivo for adults and children.
|Study Start Date:||January 2012|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Doses will be increased incrementally. Decisions to escalate the metformin dose will be made based upon tolerability of side effects as described in the schedule of evaluations to follow. All subjects will be monitored for safety while receiving metformin. Any participant with blood glucose of <60mg/dl at any time while receiving metformin will have therapy stopped and will be withdrawn from the study.
For children <50kg:
Baseline:250mg po qd, Week 2:250mg po bid, Week 4:500mg po AM/250mg po PM, Week 8:500mg po bid.
For children ≥50kg:
Baseline:500mg po qd, Week 2:500mg po bid, Week 4:1000mg po AM/500mg po PM, Week 8:1000mg po bid.
Baseline:500mg po qd,Week2:500mg po bid,Week 4:1000mg po AM/500mg po PM,Week 8:1000mg po bid.
Other Name: Glucophage, Fortamet
No Intervention: Obese Controls
Three obese but otherwise healthy adult participants will be recruited into the study as controls. These will be individuals who are not currently (or previously) on any diabetic medication including metformin.
There will be a single study visit and no medication will be administered. They will be administered a meal and pre and post-prandial blood samples will be drawn.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01876992
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Sally Radovick, MD||Johns Hopkins University Department of Medicine|