Metformin at the Cellular Level and Dosing for Diabetes Mellitus (DM)
|ClinicalTrials.gov Identifier: NCT01876992|
Recruitment Status : Terminated (All investigators/co-investigators relocating to other institutions.)
First Posted : June 13, 2013
Results First Posted : August 28, 2017
Last Update Posted : September 26, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Pre-diabetes Obesity||Drug: Metformin||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Metformin-induced CBP Phosphorylation at the Cellular Level and Corresponding Clinical Dose Response in Adults and Children|
|Study Start Date :||January 2012|
|Actual Primary Completion Date :||June 2015|
|Actual Study Completion Date :||June 2015|
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.
- % Cyclic Amine Mono Phosphate (cAMP) Response Element Binding Protein (CBP) White Blood Cell (WBC) Phosphorylation (Metformin Treated vs no Treatment) [ Time Frame: 10 weeks ]To assess metformin-induced Cyclic Amine Mono Phosphate (cAMP) response element binding protein (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.
- Change in BMI [ Time Frame: Baseline and after about 30 days ]The BMI is an index measure of body weight and is used to define states of obesity. Height ( in meters) and weight (in Kilograms) are used to calculate a BMI (kg/m2).
- Fasting Blood Glucose. [ Time Frame: 30 days ]A fasting blood sugar level less than 100 mg/dL is normal. A fasting blood sugar level from 100 to 125 mg/dL is considered prediabetes. If a subject has a blood sugar of 126 mg/dL or higher on two separate tests, they are diagnosed with diabetes. Metformin decreases fasting blood sugar.
- Effect of Dose Escalation [ Time Frame: Approximately Week 10 ]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. CBP phosphorylation will be measured by western blot analysis using a probe that is specific for the phosphorylated CBP protein. The outcome will be the % difference between the patient before starting metformin and at each dose increment.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01876992
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Sally Radovick, MD||Johns Hopkins University Department of Medicine|