Trial Outcomes & Findings for Metformin at the Cellular Level and Dosing for Diabetes Mellitus (DM) (NCT NCT01876992)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

10 participants

Primary outcome timeframe

10 weeks

Results posted on

2017-09-26

Participant Flow

Patients recruited through the Clinical Research Center.

Participant milestones

Participant milestones
Measure	Metformin 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60mg/dl at any time while receiving metformin will have therapy stopped and will be withdrawn from the study.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. Metformin	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.
Overall Study STARTED	5	5
Overall Study COMPLETED	5	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Metformin at the Cellular Level and Dosing for Diabetes Mellitus (DM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin n=5 Participants 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. Metformin	Obese Controls n=5 Participants 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.	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32 years n=5 Participants	36 years n=7 Participants	34 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Metformin n=5 Participants 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. Metformin	Obese Controls n=5 Participants 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)	15 percent phosphorylation Interval 11.0 to 18.0	9 percent phosphorylation Interval 6.0 to 12.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Metformin n=5 Participants 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. Metformin	Obese Controls n=5 Participants 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.
Change in BMI	-0.5 change in BMI (kg/m2) Interval -0.9 to 0.2	0 change in BMI (kg/m2) Interval -0.3 to 0.2

SECONDARY outcome

Timeframe: 30 days

Population: Data were not collected for this outcome measure.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately Week 10

Population: Escalating CBP phosphorylation was measured.

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.

Outcome measures

Outcome measures
Measure	Metformin n=5 Participants 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. Metformin	Obese Controls n=5 Participants 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.
Effect of Dose Escalation	21 percent phosphorylation Interval 15.0 to 25.0	8 percent phosphorylation Interval 6.0 to 10.0

Adverse Events

Metformin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Obese Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Sally Radovick

Johns Hopkins University

Phone: 7322359524

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place