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

NCT01876992 | Terminated Results DMC

• 1 other identifier: NA_00046072
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes; Pre-diabetes; Obesity

Keywords

diabetes; pediatrics; obesity; healthy volunteers; metformin; nutrition; healthy controls; bmi

Outcome Measures

Primary Outcomes (1)

• % Cyclic Amine Mono Phosphate (cAMP) Response Element Binding Protein (CBP) White Blood Cell (WBC) Phosphorylation (Metformin Treated vs no Treatment)

  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.

  10 weeks

Secondary Outcomes (2)

• Change in BMI

  Baseline and after about 30 days

• Fasting Blood Glucose.

  30 days

Other Outcomes (1)

• Effect of Dose Escalation

  Approximately Week 10

Study Arms (2)

Metformin

EXPERIMENTAL

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60mg/dl at any time while receiving metformin will have therapy stopped and will be withdrawn from the study.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.

Drug: Metformin

Obese Controls

NO INTERVENTION

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

Metformin DRUG

Also known as: Glucophage, Fortamet

Metformin

Eligibility Criteria

• Age: 10 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Children 10-17 years.
• Both genders (male and female)
• All children must have a Primary Care Physician and/or an Endocrinologist who must be aware that the child under their care will be part of the study.
• All children must have a Primary Care Physician and/or an Endocrinologist who is considering initiating metformin therapy now or in the near future as part of standard clinical care.
• Naïve to metformin.
• Either: Prediabetic children Or diabetic children under good glycemic control

You may not qualify if:

• Children ages 10-17 who do not have parental consent and/or do not give assent
• Children living in foster care
• Children with allergies to foods in the breakfast menu
• Children who currently consume any alcohol
• Children on current antidiabetic medication or those who have been on any antidiabetic medication in the 3 months prior to enrolment
• Children with a history of /or concurrent chronic disease (eg. heart, kidney, liver disease or any type of malignancy or pre-malignant condition) that required hospitalization within the last 6 months
• Pregnancy
• Refusal by a female participant who is of child bearing potential and sexually active to use contraceptive methods such as oral contraceptive pills, barrier methods and abstinence
• Children weighing less than 36 kg
• Children with any condition that increases the risk of lactic acidosis (e.g. cancer, infection, congestive heart failure, renal disease )
• Children with history of recent hospitalization for surgery, dehydration, sepsis, hypoxemia (within the past 6 months)
• Children with history of weight loss, polyuria and polydipsia
• Children who are currently enrolled in a weight management program
• Children with known hypersensitivity to metformin
• Children with a fasting blood glucose of \>180mg/dl

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus; Glucose Intolerance; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Sally Radovick
• Organization: Johns Hopkins University

sradovick@jhmi.edu

7322359524

Study Officials

• Sally Radovick, MD

  Johns Hopkins University Department of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: June 13, 2013
• Study Start: January 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 26, 2017
• Results First Posted: August 28, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)