Type1 Diabetes MellitusT1DM APNCT03353792
Using an Artificial Pancreas System in Older Adult Type 1 Diabetes Mellitus Patients
A study testing CL/AP system and usual diabetic care in people with Type1 Diabetes Mellitus, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Type1 Diabetes Mellitus
- What is being tested?
- CL/AP system and usual diabetic care
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 28 Aug 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
Official title: Restoring Brain Metabolism and Function in Older Adult T1DM Patients Using an AP System
To demonstrate that a new insulin pump system can prevent low glucose episodes and improve brain function in aged Type 1 diabetes mellitus subjects.
Read the 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.
- Conditions
- Type1 Diabetes Mellitus
- Being tested
- CL/AP system, usual diabetic care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CL/AP systemDevice
CL/AP system enabled insulin pump/CGM combination
usual diabetic careDevice
usual diabetic care (insulin pump therapy) along with CGM recording
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: usual diabetic care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: Baseline to 8 - 10 weeks
Secondary outcomes (4)
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
Measured: Baseline to 8-10 weeks
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.
Measured: Baseline to 8-10 weeks
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.
Measured: Baseline to 8-10 weeks
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.
Measured: Baseline to 8-10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2017
- Study start1 Nov 2017
- Primary completion28 Aug 2019
- Study completion28 Aug 2019
Why it stopped: Initial difficulty with recruitment was exasperated by COVID pause of the study and then the end of funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raimund Herzog, MD, Principal investigator, Yale School of Medicine Department of Endocrinology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03353792
- Sponsor's protocol ID
- 2000020059
- Other IDs
- 1R01DK101984-01A1, 1DP3DK112227-01
- Acronym
- T1DM AP
- Status last verified
- Nov 2022
- First submitted
- 9 Nov 2017
- Last updated
- 18 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoring Brain Metabolism and Function in Older Adult T1DM Patients Using an AP System
- ClinicalTrials.gov ID
- NCT03353792
- Acronym / sponsor ID
- T1DM AP / 2000020059
- Conditions
- Type1 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Initial difficulty with recruitment was exasperated by COVID pause of the study and then the end of funding.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 28 Aug 2019 (actual)
- Study completion
- 28 Aug 2019 (actual)
- First posted
- 27 Nov 2017 (actual)
- Results
- Posted 28 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| CL/AP system | Active comparator | Device: CL/AP systemTo 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. |
| usual care | Placebo comparator | Device: usual diabetic careSubjects in this control group will continue their usual diabetic care (insulin pump therapy) along with CGM recording. |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CL/AP systemCL/AP system enabled insulin pump/CGM combination | Device | CL/AP system |
| usual diabetic careusual diabetic care (insulin pump therapy) along with CGM recording | Device | usual care |
Primary outcome
Brain Alternate Fuel Uptake
Time frame: Baseline to 8 - 10 weeks
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."
4 secondary outcomes
Change in Cognitive Function: MOCA
Time frame: Baseline to 8-10 weeks
Change in Cognitive Function: Trail Test A
Time frame: Baseline to 8-10 weeks
Change in Cognitive Function: Trail Test B
Time frame: Baseline to 8-10 weeks
Change in Cognitive Function: Grooved Pegboard Test
Time frame: Baseline to 8-10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raimund Herzog, MD principal investigator
Yale School of Medicine Department of Endocrinology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CL/AP system and usual diabetic care in people with Type1 Diabetes Mellitus, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain Alternate Fuel Uptake (time frame: Baseline to 8 - 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2022.