Using an Artificial Pancreas System in Older Adult Type 1 Diabetes Mellitus Patients

NCT03353792 | Terminated Results DMC FDA Device

• 3 other identifiers: 20000200591R01DK101984-01A11DP3DK112227-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

To demonstrate that a new insulin pump system can prevent low glucose episodes and improve brain function in aged Type 1 diabetes mellitus subjects.

Conditions

Type1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Brain Alternate Fuel Uptake

  Change in brain alternate fuel uptake under hypoglycemia was measured by assessing the percent enrichment of Glutamine 4 (Gln4). Change was measured by subtracting follow up from baseline. Astrocytic glutamine C4 enrichment is a measure of brain acetate metabolism (an alternate fuel to glucose). Previous studies have shown that in people who have been exposed to frequent hypoglycemic episodes, glutamine C4 enrichment increases. Therefore, we expected a reduction in Glutamine C4 percent enrichment in the follow up NMR scans in the intervention group who avoided frequent hypoglycemic episodes through the CL/AP system. In addition, there is no specific cut off value used for Glutamine C4 enrichment, rather a change or reduction was expected and noted."

  Baseline to 8 - 10 weeks

Secondary Outcomes (4)

• Change in Cognitive Function: MOCA

  Baseline to 8-10 weeks

• Change in Cognitive Function: Trail Test A

  Baseline to 8-10 weeks

• Change in Cognitive Function: Trail Test B

  Baseline to 8-10 weeks

• Change in Cognitive Function: Grooved Pegboard Test

  Baseline to 8-10 weeks

Study Arms (2)

CL/AP system

ACTIVE COMPARATOR

To improved glycemic control and strict avoidance of hypoglycemia via 8-week use of a CL/AP system (closed-loop/artificial pancreas) reverses brain metabolic adaptations in older adult T1DM patients.

Device: CL/AP system

usual care

PLACEBO COMPARATOR

Subjects in this control group will continue their usual diabetic care (insulin pump therapy) along with CGM recording.

Device: usual diabetic care

Interventions

CL/AP system DEVICE

CL/AP system enabled insulin pump/CGM combination

CL/AP system

usual diabetic care DEVICE

usual diabetic care (insulin pump therapy) along with CGM recording

usual care

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed and dated informed consent form
• Male or female
• Age 50-75 years (at least 50% over the age of 65)
• T1DM (\>20 years duration)
• C-peptide undetectable
• HbA1c of \< 8%
• Insulin pump therapy
• History of frequent hypoglycemia with unawareness (defined as 2 or more episodes of severe hypoglycemia within one year requiring assistance) and 2 or more glucose values \< 54 mg/dL during the week of Continuous Glucose Monitoring (CGM) (iPRO monitor, Medtronic) prior to enrollment
• BMI \<27 kg/m2
• Good general health as evidenced by medical history and blood screening
• Willing to comply with all study procedures and be available for the duration of the study
• Willing to fast for a limited time period on the morning of a clamp study

You may not qualify if:

• Significant diabetic complications (untreated proliferative retinopathy, creatinine ≥1.5 mg/dl, urinary albumin levels 300 mg/day, autonomic neuropathy, painful peripheral neuropathy)
• Significant alcohol intake and vegetarian diet since both are known to have an impact on counterregulation and brain metabolism
• Any contraindications for MRI scanning, including presence of metallic implants or claustrophobia.
• Heavy exercise on a regular basis (i.e. marathon runners)
• Known allergic reactions to components of the study product(s)
• Treatment with another investigational drug or other intervention
• Active infection including hepatitis C, hepatitis B, HIV
• Any past or current history of alcohol or substance abuse
• Psychiatric or neurological disorders under active treatment
• Baseline hemoglobin \< 10.5 g/dL in females, or \< 12.5 g/dL in males. Blood donation within 30 days of the study
• History of coagulopathy or medical condition requiring long-term anticoagulant therapy (low-dose aspirin treatment is allowed)
• Co-existing cardiac, liver, and kidney disease
• Abnormal liver function tests
• Women that are on oral contraceptives, post-menopausal, pregnant (as assessed by pregnancy test that will be performed on female participants at reproductive age), or lactating.
• Any medical condition or medication that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Limitations and Caveats

This study experienced low enrollment prior to being paused due to COVID19. Upon restart of the study, it was determined that there were not sufficient funds to fully resume the trial. The overall enrollment did not provide adequate numbers to perform statistical analyses outside of providing summary statistics on those that were enrolled and those that completed the study.

Results Point of Contact

• Title: Raimund Herzog, MD, MHS
• Organization: Associate Professor of Medicine

raimund.herzog@yale.edu

(877) 925-3637

Study Officials

• Raimund Herzog, MD

  Yale School of Medicine Department of Endocrinology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The intervention consists of treatment with a CL/AP-enabled insulin pump/CGM combination; subjects in the control group will continue their usual diabetes care (insulin pump therapy) along with CGM recording .
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The design is a single-site, parallel group, randomized clinical trail. Following enrollement and CGM documentation of hypoglycemia during the 4-week run-in period, study participants are randomized to intervention and control groups.

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 27, 2017
• Study Start: November 1, 2017
• Primary Completion: August 28, 2019
• Study Completion: August 28, 2019
• Last Updated: November 18, 2022
• Results First Posted: October 28, 2022

Record last verified: 2022-11

Locations

US (1)