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Using an Artificial Pancreas System in Older Adult Type 1 Diabetes Mellitus Patients (T1DM AP)

Primary Purpose

Type1 Diabetes Mellitus

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
CL/AP system
usual diabetic care
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type1 Diabetes Mellitus

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Yale New Haven Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

CL/AP system

usual care

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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."

Secondary Outcome Measures

Change in Cognitive Function: MOCA
The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal. Change was calculated by subtracting follow up from baseline. https://www.parkinsons.va.gov/resources/MoCA-Instructions-English.pdf
Change in Cognitive Function: Trail Test A
Trail making test (TMT) A is a test of visual attention and task switching. It provides information about visual search speed, speed of processing and executive function. Time is measured in seconds. The typical average time to complete the test is 29 seconds, a "deficient" performance would be >78 seconds; most people are able to complete in 90 seconds. Change was calculated by subtracting follow up from baseline.
Change in Cognitive Function: Trail Test B
Trail making test (TMT) B is a test of visual attention and task switching. It provides information about visual search speed, speed of processing and executive function. Time will be measured in seconds. The typical average time to complete the test is 75 seconds, a "deficient" performance would be >273 seconds; most people are able to complete in 180 seconds. Change was calculated by subtracting follow up from baseline.
Change in Cognitive Function: Grooved Pegboard Test
The grooved pegboard test is a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consists of a small board of holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. The task was completed using the dominant hand. Time was measured in seconds.

Full Information

First Posted
November 9, 2017
Last Updated
November 16, 2022
Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03353792
Brief Title
Using an Artificial Pancreas System in Older Adult Type 1 Diabetes Mellitus Patients
Acronym
T1DM AP
Official Title
Restoring Brain Metabolism and Function in Older Adult T1DM Patients Using an AP System
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Initial difficulty with recruitment was exasperated by COVID pause of the study and then the end of funding.
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
August 28, 2019 (Actual)
Study Completion Date
August 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The goals of this proposal are to implement a Close-Loop/Artificial Pancreas (CL/AP) system in older patients with type 1 diabetes mellitus (T1DM) in order to reverse brain metabolic adaptations and restore metabolic sensitivity, hypoglycemia awareness and appropriate hormonal counterregulatory responses (CRR). For purposes of this study we are looking to enroll aged T1DM subjects under insulin pump treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes Mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
Participant
Masking Description
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 .
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CL/AP system
Arm Type
Active Comparator
Arm Description
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.
Arm Title
usual care
Arm Type
Placebo Comparator
Arm Description
Subjects in this control group will continue their usual diabetic care (insulin pump therapy) along with CGM recording.
Intervention Type
Device
Intervention Name(s)
CL/AP system
Intervention Description
CL/AP system enabled insulin pump/CGM combination
Intervention Type
Device
Intervention Name(s)
usual diabetic care
Intervention Description
usual diabetic care (insulin pump therapy) along with CGM recording
Primary Outcome Measure Information:
Title
Brain Alternate Fuel Uptake
Description
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."
Time Frame
Baseline to 8 - 10 weeks
Secondary Outcome Measure Information:
Title
Change in Cognitive Function: MOCA
Description
The Montreal Cognitive Assessment (MoCA) was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal. Change was calculated by subtracting follow up from baseline. https://www.parkinsons.va.gov/resources/MoCA-Instructions-English.pdf
Time Frame
Baseline to 8-10 weeks
Title
Change in Cognitive Function: Trail Test A
Description
Trail making test (TMT) A is a test of visual attention and task switching. It provides information about visual search speed, speed of processing and executive function. Time is measured in seconds. The typical average time to complete the test is 29 seconds, a "deficient" performance would be >78 seconds; most people are able to complete in 90 seconds. Change was calculated by subtracting follow up from baseline.
Time Frame
Baseline to 8-10 weeks
Title
Change in Cognitive Function: Trail Test B
Description
Trail making test (TMT) B is a test of visual attention and task switching. It provides information about visual search speed, speed of processing and executive function. Time will be measured in seconds. The typical average time to complete the test is 75 seconds, a "deficient" performance would be >273 seconds; most people are able to complete in 180 seconds. Change was calculated by subtracting follow up from baseline.
Time Frame
Baseline to 8-10 weeks
Title
Change in Cognitive Function: Grooved Pegboard Test
Description
The grooved pegboard test is a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consists of a small board of holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. The task was completed using the dominant hand. Time was measured in seconds.
Time Frame
Baseline to 8-10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raimund Herzog, MD
Organizational Affiliation
Yale School of Medicine Department of Endocrinology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States

12. IPD Sharing Statement

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

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