Diabetes Mellitus, Type 1NCT03392441
Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes
A study testing Insulin Deprivation in Type 1 Diabetic Patients in people with Diabetes Mellitus, Type 1 and Diabetes, run by Mayo Clinic at 1 site in United States.
Trial summary
What are the effects of transient insulin deprivation on brain structure, blood flow, mitochondrial function, and cognitive function in T1DM patients? What are the effects of transient insulin deprivation on circulating exosomes and metabolites in T1DM patients? Read more about this study
- Who is it for?
- Ages 14 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1, Diabetes, Diabetes Complications
- What is being tested?
- Insulin Deprivation in Type 1 Diabetic Patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to 5 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 14 to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Male and females age 14-17 years, females must be post-menarcheal
- Age 18-45 years
- Able to provide written consent
- Parents able to provide written consent
- T1DM treated with CSII or MDI (not degludec)
Who cannot join
- BMI < 20 or > 30 kg/m2
- BMI z-score <5th or >95th percentile
- Celiac disease
- Pregnancy
- Smoking
- Reported history of illicit substance use
Show all 15Show fewer
- History of active cardiovascular, cerebrovascular, or peripheral vascular disease
- Active renal disease evidenced by estimated GFR < 50 mL/min/1.73 m2
- History of traumatic brain injury
- Dementia or any other neurologic disease
- Psychiatric disease\
- Any learning disability
- Hemoglobin A1c > 8.5%
- Hemoglobin A1c > 9%
- T2DM, or impaired fasting glucose
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Pilot Study to Evaluate the Effects of Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes
What are the effects of transient insulin deprivation on brain structure, blood flow, mitochondrial function, and cognitive function in T1DM patients?
What are the effects of transient insulin deprivation on circulating exosomes and metabolites in T1DM patients?
Read the detailed description
Diabetes is associated with impaired cognition, abnormal brain development in children, and dementia in older adults, however the underlying mechanisms remain unclear. Little is known about the brain-specific effects of acute insulin deficiency. Our recent studies in diabetic mice show an overall down regulation of brain mitochondrial ATP production and up regulation of several key mitochondrial proteins, indicating that insulin withdrawal has a profound effect on brain mitochondria as well as proteins implicated in neurodegeneration. Hyperglycemia is known to alter cognitive function, but it is unclear if insulin deprivation independently alters cognitive function and has not been assessed in humans.
In order to investigate the effects of insulin deprivation on the human brain, we propose a study involving temporary insulin deprivation in adolescents and adults with type 1 diabetes (T1DM). We will perform brain MRI, phosphorus31 spectroscopy, cognitive testing, circulating blood exosome measurements, and proteomics from muscle biopsy; comparing these measures during insulin treatment and deprivation between diabetic patients and age-, sex-, BMI-matched controls.
Specific aim 1: Determine whether transient insulin deprivation in T1DM adults and adolescents alters brain structure, functions and blood flow as assessed by structural/functional MRI.
Specific aim 2: Determine whether transient insulin deprivation in T1DM adults and adolescents alters cognitive function.
Specific aim 3: Determine whether transient insulin deprivation in T1DM adults and adolescents alters the circulating blood exosome contents and metabolome that can potentially impact brain functions.
Specific aim 4: Determine whether transient insulin deprivation in T1DM adults alters the skeletal muscle proteome homeostasis especially those involved in fission and fusion
- Conditions
- Diabetes Mellitus, Type 1, Diabetes, Diabetes Complications
- Being tested
- Insulin Deprivation in Type 1 Diabetic Patients
- Keywords
- dementia, cognition, insulin, adolescent
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Diabetes Complications, Dementia, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin Deprivation in Type 1 Diabetic PatientsOther
Type 1 Diabetic Patients requiring insulin will have insulin stopped for a short period of time (4-6 hours)
| Study group | Role | What they receive |
|---|---|---|
| Insulin Deprivation | Experimental | Insulin Deprivation in Type 1 Diabetic Patients will be performed for a short time period (4-6 hours). Changes to Age, Sex, and Gender matched controls will be compared. Receives: Other: Insulin Deprivation in Type 1 Diabetic Patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Structural MRI
Structural magnetic resonance imaging (MRI) is a non-invasive technique for examining the anatomy and pathology of the brain (as opposed to using functional magnetic resonance imaging [fMRI] to examine brain activity. This produces images which can be used for clinical radiological reporting as well as for detailed analysis.
Measured: baseline, 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2018
- Study start30 Nov 2017
- Primary completion1 Aug 2018
- Study completion5 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, K. Sreekumaran Nair, Mayo Clinic
- Investigators
- K Sreekumaran Nair, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03392441
- Sponsor's protocol ID
- 17-005244
- Status last verified
- Feb 2022
- First submitted
- 13 Dec 2017
- Last updated
- 3 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Creo AL, Cortes TM, Jo HJ, Huebner AR, Dasari S, Tillema JM, Lteif AN, Klaus KA, Ruegsegger GN, Kudva YC, Petersen RC, Port JD, Nair KS. Brain functions and cognition on transient insulin deprivation in type 1 diabetes. JCI Insight. 2021 Mar 8;6(5):e144014. doi: 10.1172/jci.insight.144014.
PubMed 33561011
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate the Effects of Insulin Deprivation on Brain Structure and Function in Humans With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03392441
- Acronym / sponsor ID
- 17-005244
- Conditions
- Diabetes Mellitus, Type 1, Diabetes, Diabetes Complications
- Keywords
- dementia, cognition, insulin, adolescent
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 1 Aug 2018 (actual)
- Study completion
- 5 Jul 2019 (actual)
- First posted
- 8 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
What are the effects of transient insulin deprivation on brain structure, blood flow, mitochondrial function, and cognitive function in T1DM patients?
What are the effects of transient insulin deprivation on circulating exosomes and metabolites in T1DM patients?
Detailed description
Diabetes is associated with impaired cognition, abnormal brain development in children, and dementia in older adults, however the underlying mechanisms remain unclear. Little is known about the brain-specific effects of acute insulin deficiency. Our recent studies in diabetic mice show an overall down regulation of brain mitochondrial ATP production and up regulation of several key mitochondrial proteins, indicating that insulin withdrawal has a profound effect on brain mitochondria as well as proteins implicated in neurodegeneration. Hyperglycemia is known to alter cognitive function, but it is unclear if insulin deprivation independently alters cognitive function and has not been assessed in humans.
In order to investigate the effects of insulin deprivation on the human brain, we propose a study involving temporary insulin deprivation in adolescents and adults with type 1 diabetes (T1DM). We will perform brain MRI, phosphorus31 spectroscopy, cognitive testing, circulating blood exosome measurements, and proteomics from muscle biopsy; comparing these measures during insulin treatment and deprivation between diabetic patients and age-, sex-, BMI-matched controls.
Specific aim 1: Determine whether transient insulin deprivation in T1DM adults and adolescents alters brain structure, functions and blood flow as assessed by structural/functional MRI.
Specific aim 2: Determine whether transient insulin deprivation in T1DM adults and adolescents alters cognitive function.
Specific aim 3: Determine whether transient insulin deprivation in T1DM adults and adolescents alters the circulating blood exosome contents and metabolome that can potentially impact brain functions.
Specific aim 4: Determine whether transient insulin deprivation in T1DM adults alters the skeletal muscle proteome homeostasis especially those involved in fission and fusion
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Insulin Deprivation | Experimental | Other: Insulin Deprivation in Type 1 Diabetic PatientsInsulin Deprivation in Type 1 Diabetic Patients will be performed for a short time period (4-6 hours). Changes to Age, Sex, and Gender matched controls will be compared. |
Who may qualify
- Ages
- 14 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Male and females age 14-17 years, females must be post-menarcheal
- Age 18-45 years
- Able to provide written consent
- Parents able to provide written consent
- T1DM treated with CSII or MDI (not degludec)
Key exclusion criteria (15 listed)
- BMI < 20 or > 30 kg/m2
- BMI z-score <5th or >95th percentile
- Celiac disease
- Pregnancy
- Smoking
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 |
|---|---|---|
| Insulin Deprivation in Type 1 Diabetic PatientsType 1 Diabetic Patients requiring insulin will have insulin stopped for a short period of time (4-6 hours) | Other | Insulin Deprivation |
Primary outcome
Change in Structural MRI
Time frame: baseline, 6 hours
Structural magnetic resonance imaging (MRI) is a non-invasive technique for examining the anatomy and pathology of the brain (as opposed to using functional magnetic resonance imaging [fMRI] to examine brain activity. This produces images which can be used for clinical radiological reporting as well as for detailed analysis.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2022.
- Derived from this study: PubMed 33561011Creo AL, Cortes TM, Jo HJ, Huebner AR, Dasari S, Tillema JM, Lteif AN, Klaus KA, Ruegsegger GN, Kudva YC, Petersen RC, Port JD, Nair KS. Brain functions and cognition on transient insulin deprivation in type 1 diabetes. JCI Insight. 2021 Mar 8;6(5):e144014. doi: 10.1172/jci.insight.144014.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
K Sreekumaran Nair principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insulin Deprivation in Type 1 Diabetic Patients in people with Diabetes Mellitus, Type 1 and Diabetes, run by Mayo Clinic 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 5 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: finished, as of the sponsor's last update on 3 Feb 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Structural MRI (time frame: baseline, 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03392441, which also lists 1 linked publication.
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 3 Feb 2022; AzTrials last refreshed its copy on 31 Oct 2026.