Individualizing Automated Closed Loop Glucose Control Through Pharmacokinetic Profiling in an Insulin-Only Bionic Pancreas

What Was Tested

This registered phase 2, phase 3 trial tested Insulin Aspart and Insulin Lispro.

Subjects will participate in three weeks of the bionic pancreas in the insulin-only configuration.

Each week, subjects will use a different rapid acting insulin analog -- Humalog, Novolog, or BC222 insulin lispro -- in a randomized cross-over order.

It had three arms (groups): Bionic Pancreas - Humalog (experimental), Bionic Pancreas - Novolog (experimental) and Bionic Pancreas - BC222 insulin lispro (experimental).

Subjects will participate in one week of wearing the insulin only bionic pancreas using humalog as the rapid acting insulin.

Subjects will participate in one week of wearing the insulin only bionic pancreas using novolog as the rapid acting insulin.

Subjects will participate in one week of wearing the insulin only bionic pancreas using BC222 insulin lispro as the rapid acting insulin.

The registry classes the interventions as device and drug.

More on the Plan

The investigators hypothesize that differences in the PK characteristics of insulin analogs will lead to differences in glycemic outcomes when delivered by the insulin-only configuration of the bionic pancreas.

Specifically, the investigators predict that insulin analogs that have faster absorption (numerically lower Tmax and/or T½max) and insulin analogs that have faster clearance (numerically lower terminal half-life) will result in lower mean glucose and/or a lower percentage of time in the hypoglycemic range.

Up to 30 subjects will participate in three 7-day study arms using insulin lispro, insulin aspart, and BC222 lispro in the bionic pancreas in random order.

Who Took Part

The registry lists 20 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Age ≥ 18 years and have had clinical type 1 diabetes for at least one year. Diabetes managed using an insulin pump for ≥ 6 months. Have used a CGM for at least one cumulative month over the last 12 months. Willing to remain within a 250 mile radius of MGH. No air travel will be allowed, and subjects will still be expected to follow the visit schedule as described. Willing to wear one Dexcom CGM sensor, and one leur-lock compatible infusion set that must be replaced every other day.

The full record lists 7 inclusion and 25 exclusion criteria; among the exclusions: unable to provide informed consent (e.g. impaired cognition or judgment); renal failure requiring dialysis; personal history of cystic fibrosis, severe pancreatitis, pancreatic tumor, pancreatectomy or any other pancreatic disease leading to diabetes mellitus.

How the Study Was Run

It was run as a randomized, crossover and single-blind study.

The participants were allocated by chance, so the Insulin Aspart group and the comparison group should start out alike.

In the crossover set-up each of the participants took both Insulin Aspart and the comparison in turn, acting as their own control.

In this single-blind Insulin Aspart study one party knew the assignments and the other did not.

Those kept unaware of assignments: participant.

It started in 2019-03-19 with completion listed for 2019-07-23.

It ran at 1 site in United States.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Average Continuous Glucose Monitor (CGM) Glucose (time frame: 7 days).

It also tracked 6 secondary outcomes, for example Percentage of Time Spent Within Each of the Following Ranges:, Within Day Coefficient of Variation, Mean Post Prandial Excursion, Number of Symptomatic Hypoglycemic Events Per Day and Grams of Carbohydrates Consumed to Treat Hypoglycemia Per Day.

What This Means in Plain Language

Put simply, this is a phase 2, phase 3, randomized trial of Insulin Aspart and Insulin Lispro in 20 people.

Its size is small, so on its own it can only give an early look.

It ended early (terminated); results are posted on the registry, and this page does not restate them.

More context: the Insulin Aspart compound page and the Insulin Lispro compound page, all human trials.