Clinical trial NCT01876992
Conditions: Diabetes Pre-diabetes Obesity
Keywords: diabetes pediatrics obesity healthy volunteers metformin nutrition healthy controls bmi
Sponsor: Johns Hopkins University
Start date: 2012-01-01; Completion date: 2015-06-01
Enrollment: 10 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators know that metformin works at the level of the cells in the body by acting on a protein called Cyclic amine monophosphate- Response Binding Elements (CREB) binding protein or Constitutive Reverter of eIF2α Phosphorylation (CREP) Binding Protein (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.

Detailed description:
Our studies have shown that metformin acts at the cellular level by acting on a target protein, Cyclic amine monophosphate-Response Binding Elements (CREB) binding protein or CREP Binding Protein (CBP). Patients are treated with many different doses of metformin, some patients respond well to low doses while others require much higher doses. The investigators do not understand why this may be and are interested in knowing if the investigators can treat patents effectively with low doses. What the investigators do not know is how this process is affected when the dose of the metformin is increased or changed. Changes in metformin's target protein will provide evidence on the effectiveness of the dose.

Also, 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.

Arms: arm 1: 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.

For adults:

Baseline:500mg po qd,Week2:500mg po bid,Week 4:1000mg po am/500mg po pm,Week 8:1000mg po bid. arm 2: 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.
Interventions: intervention 1: Metformin
Intervention descriptions: intervention 1: None

Protocol documents: