A Pilot Study to Evaluate the Safety of Terbutaline in Children With Type 1 Diabetes

Approximately 10 children will be recruited from five centers in the United States to participate in this study. The data collected in this pilot study will be used to determine whether to proceed to a randomized trial using the dose of terbutaline being used in the pilot study or the need for additional pilot testing with a lower dose of terbutaline.

Beginning the Study

When a chid enters the study, the following will be done:

1. After eligibility is determined, informed consent and assent are obtained from the parent/guardian and subject.
2. An unblinded CGM will be used and blood ketones will be checked each morning by the subject for at least one week. Subjects may be asked to wear an Actiwatch monitor each night.
3. Terbutaline will be initiated during a CRC admission and continued following the CRC stay for 21-28 days.

• Subjects weighing between 25 and 45 kg will be treated with a nightly oral dose of 2.5 mg and subjects who weigh more than 45 kg will be treated with 3.75 mg.

1. The CRC admission will last approximately 18-20 hours and include the following:

• Monitoring of effects of terbutaline by measurement of heart rate, blood pressure, blood and interstitial glucose, lactate, ketones, NEFA, B-OH butyrate
• Assessment of the accuracy of the CGM by comparing sensor glucose values to blood glucose values

1. The outpatient phase will last 21-28 days and include the following:

• Nightly use of terbutaline as described above
• Use of an unblinded CGM on a daily basis to monitor the glucose levels
• Subjects may be asked to wear the Actiwatch monitor overnight
• Measurement of blood ketones each morning
• Phone calls to each subject on the first outpatient day of terbutaline use and then approximately every 3 days (twice a week) until the end of the subject's follow up.

1. Second CRC admission to mirror the first admission between 21 and 28 days after initiation of terbutaline
2. Follow up for 1-2 weeks after discontinuation of terbutaline until glucose control is back to prestudy level.

Procedures at home after hospital stay

1. Terbutaline will be taken orally each day prior to bedtime.
2. Each subject will continue to use a CGM, with instructions to use it as close to 24/7 as possible.
3. Prior to each phone call, the subject will be instructed to download the CGM and either email or fax the file to the clinic so that the glucose data can be reviewed during the phone contacts.
4. Each subject will be provided with an HGM and test strips. The HGM will be used for calibration of the CGM and to confirm high and low values on the CGM prior to acting on them. It will be downloaded at the end-of-study CRC admission. The subject will be asked to measure blood ketones each morning using the meter and strips that will be provided.
5. Each subject may be asked to wear an Actiwatch each night to measure movement while the subject is sleeping.
6. Phone calls to each subject will be made after the first outpatient day of terbutaline use and then approximately every 3 days (twice a week) until the end of the subject's follow up plus an about 7 days after terbutaline is discontinued.
7. Prior to the end-of-study CRC admission, follow-up visits can occur at any time at the discretion of the investigator.

End of study admission

The end-of study CRC admission will occur after 21-28 days of the outpatient phase.The protocol will be identical to the protocol for the first CRC admission. The dinner and breakfast meals will be identical to the meals given during the first admission.

The sensors will be removed prior to discharge, unless the investigator decides it would be beneficial to continue a CGM for 1-2 weeks to assist in the maintenance of glucose control after terbutaline has been stopped.