IRB Number:

05-004002

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

This study is being done to determine the effects of Pioglitazone (Actos) and Metformin on muscle metabolism.

Who is Eligible to Participate in the Study?

Men and women (over 20 years old) who are overweight and have a fasting blood glucose of 100-180mg/dL (borderline diabetes or diet-controlled diabetes

Minimum Age:

20

What is Involved With this Study?

Before enrollment in the study, you will have two screening exams to determine if you are eligible for the study. The first screening will include a blood test to check your glucose (blood sugar) and a complete medical exam.

The second screening exam will include an ECG, urine test and blood test to ensure that you do not have any unknown medical problems. You will talk to a dietitian to discuss dietary needs during the study. Measurement of your body muscle, bone and fat content will be performed using dual x-ray densitometry (DEXA). During this test, you will lie on an examining table, while a low-intensity x-ray scans your entire body. The measurement takes 20 minutes.

If you are eligible for the study, you will be put in one of 2 groups by chance (as in the flip of a coin). One group will take the medications, Pioglitazone and Metformin for 3 months and the other group will take a placebo (sugar pill) for 3 months. You will be scheduled an overnight stay at the GCRC before starting the medication and after immediately after finishing the 3 months of medication. You will need to take the medications twice a day with breakfast and supper.

For each overnight stay, the following will happen:

1. Three days prior to admission, all of your food will be provided by the GCRC. You will also need to stop taking any aspirin and/or ibuprofen until 3 days after the overnight visit.

2. You will be admitted as an inpatient to the GCRC at around 5:00 p.m. and remain at the GCRC until 4:00 p.m. the following day.

3. After you arrive at the GCRC, you will eat a meal at approximately 6:00 p.m., late snack at around 10:00 p.m., then fast (go without food) until after testing the next day at about 3:15 p.m. You may drink up to one quart of water during this time. You will be given a meal before your dismissal from the GCRC.

4. At approximately 9:00 p.m., an intravenous (IV or small tube in the vein) line will be placed in one forearm. This line will be used for the infusion of saline (salt water).

5. A second intravenous line will be placed in a vein on the back of your hand. This line will be used to collect blood samples during the evening and throughout the next day.

6. At approximately 4:00am, a labeled glucose isotope infusion (IV bag of liquid) will be given into your intravenous line. The labeled glucose is a stable, non-radioactive sugar that will allow us to follow the movement of sugars into the cells.

7. At 5:45 a.m. on the morning following the admission, you will be asked to start a urine collection. Your urine will be collected any time you need to go to the bathroom until approximately 3 p.m.

8. A second intravenous line will be placed in a vein on the back of your hand. This line will be used to collect blood samples during the evening and throughout the next day. The hand with the second IV line will be kept in a 'hot box'. The 'hot box' is a large plastic box that blows warm air over your hand. The temperature will not be greater than 120F. The 'hot box' is intended to make blood flow through the skin so it will cause some reddening of the skin and mild discomfort. This will go away when your hand is taken out of the 'hot box'.

9. At approximately 7:00 a.m., a small piece of muscle will be taken from your thigh using a special needle. A local anesthetic (numbing medicine) will first be injected, then a small incision (1/4) will be made in order to insert the needle. Suction will be applied and then a small piece of muscle will be withdrawn. After the biopsy, pressure will be applied on the biopsy site until any bleeding stops. Bandage strips will be used to close the wound. A pressure bandage will be applied for 5 hours. You may walk immediately after the biopsy, but it is recommended that you not perform any strenuous activities for 48 hours. This wound is usually completely healed in about five days.

10. Immediately after the first biopsy, you will be given four more different infusions (IV bags of liquid) that will continue until approximately 3:00 p.m.:

• insulin (a hormone that allows your body to use sugar and amino acids)


• glucose (the sugar found in your blood)


• amino acids (make up very basic parts of cells also known as the nutrient building blocks of protein)


• amino acid isotope (this is a non-radioactive marker or label of amino acids which allows us to study the amino acids in the muscle)

11. During the study period, blood samples will be collected from your hand vein every 10 minutes. The total amount collected will be approximately 325ml (less than 1 cup) during this visit.

12. Three hours after the start of the infusions, a second muscle biopsy will be done on the same leg but in a different spot. Eight hours after the start of the infusions a third muscle biopsy will be done on the opposite leg. The same procedure will be followed for all biopsies.

13. You will be asked to wear a plastic hood for 45 minutes during the study period in order to collect breath samples.

14. After the biopsy is completed, you will be given a meal and the infusions stopped. You will be discharged from the General Clinical Research Center at approximately 4:00 p.m.

You will begin taking your medications within at least 2 weeks after you complete the study day. Once each month, while you are taking the medications you will need to come to the GCRC for a blood draw, weight check and to get your next month?s set of medications. After 3 months of taking the medication, you will repeat the DEXA, the meals days and overnight visit to the GCRC.

How long will the Study run?

You will be in the study for approximately 4 months or until you complete the second overnight stay.

Who can I Contact for Additional Information on this Trial?

Contact Deb Sheldon (507-255-8082) or email sheldon.deborah@mayo.edu

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 09/14/2006