Diabetes Mellitus, Type 1NCT00590876
The Impact of Pancreatic Islet Cell Allotransplantation on Cognitive Function in Type 1 Diabetes Mellitus
An observational study of Diabetes Mellitus, Type 1, run by Yale University at 2 sites in United States.
Trial summary
In patients with Type 1 Diabetes Mellitus, hypoglycemia (low blood sugar) is the rate-limiting step to achieve glucose level control. As a result, understanding the body's responses (including the brain's response) to hypoglycemia is essential for the effective treatment of patients with T1DM. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 1
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2008to Jul 2011
- Phase
- Observational
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Patients undergoing pancreatic islet cell allotransplantation at the University of Minnesota Patients who are seen at Diabetes Clinics at Yale School of Medicine Nondiabetic, healthy subjects from New Haven and surrounding communities
Who may be able to join
- T1DM subjects must be 18 years or older and able to provide written consent
- T1DM subjects must be undergoing intensive management, defined by self-monitoring of glucose values 3 or more times each day and by the administration of 3 or more insulin injections each day (or the use of insulin pump therapy). This clinical management must be monitored in close cooperation with an endocrinologist as defined by at least 3 contacts during the previous 12 months.
- T1DM subjects must demonstrate at least one of the following situations that persist despite intensive insulin management efforts:
- metabolic lability/instability, characterized by either 2 or more episodes of severe hypoglycemia within one year (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person, and which is associated with a blood glucose of < 50 mg/dl or prompt recovery after administration of oral carbohydrate, intravenous glucose, or glucagon) or 2 or more hospital admissions for diabetic ketoacidosis over the last year.
- reduced awareness of hypoglycemia (defined by a specific hypoglycemia questionnaire)
- Fasting glucose < 110 mg/dl and otherwise healthy
- Age > 18 years
- Body weight parameters the same as for subjects with diabetes (above)
Who cannot join
- Age < 18 years
- Body weight > 75 kg at screening
- BMI > 24 (female) and > 25 (male) kg/m2
- Waist to hip ratio greater than or equal to 0.80 (female) and greater than or equal to 0.95 (male)
- Insulin requirement of > 0.7IU/kg/day or > 50 IU per day, whichever is less
- Positive C-peptide response to intravenous arginine stimulation (5g): any C-peptide greater than or equal to 0.2ng/ml at 2, 3, 4, 5, 7, and 10 minutes post infusion
Show all 46Show fewer
- Untreated proliferative retinopathy
- Creatinine clearance < 75ml/min/1.73 m2
- Serum creatinine greater than or equal to 1.3 mg/dl for females, and greater than or equal to 1.5 mg/dl for males
- Previous pancreas or islet cell transplant
- Presence of history of panel-reactive anti-HLA antibodies > 10%
- Positive pregnancy test or presently breast-feeding, or failure to follow effective contraceptive measures or abstinence (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condom use alone is not acceptable.)
- Active infection including Hepatitis C, Hepatitis B, HIV, or Tuberculosis (or under treatment for suspected Tuberculosis)
- Negative screen for Epstein-Barr Virus (EBV) or by an EBNA method
- Invasive aspergillus infection within a year prior to study entry
- Any history of malignancy except for adequately treated squamous cell or basal cell carcinoma of the skin
- Active alcohol or substance abuse which includes cigarette smoking (must be abstinent for 6 months). Active alcohol use abuse should be considered using the current NIAAA definitions whereby alcohol abuse is defined by a pattern of drinking that is accompanied by one or more of the following situations within a 12-month period:
- Failure to fulfill major work, school, or home responsibilities
- Drinking in situations that are physically dangerous, such as while driving a car or operating machinery
- Recurring alcohol-related legal problem, such as being arrested for driving under the influence of alcohol or for physically hurting someone while drunk
- Continued drinking despite having ongoing relationship problems that are caused or worsened by the effects of alcohol
- History of nonadherence to prescribed regimens
- Psychiatric disorder making the subject not a suitable candidate for transplantation (for those who are undergoing islet cell allotransplantation).
- Inability to provide informed consent
- Baseline Hgb < 11.7 g/dl in females, or < 13 g/dl in males; lymphopenia (< 1 ,000 lymphocytes/mcl) or leukopenia (< 3,000 total leukocytes/mcl), or an absolute CD4 count < 500, or platelets < 150,000
- History of coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after transplantation (low-dose aspirin treatment is allowed) or patient with INR > 1.5
- Severe co-existing cardiac disease, characterized by any one of the following conditions:
- recent myocardial infarction (within the past 6 months) or
- angiographic evidence of non-correctable coronary artery disease, or
- evidence of ischemia on functional cardiac exam (to be repeated annually)or
- left ventricular ejection fraction < 30%
- Baseline liver function tests outside of normal range or a history of significant liver disease
- Presence of gallstones or hemangioma in the liver on baseline ultrasound exam
- Active peptic ulcer disease
- Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- Presence of severe allergy requiring acute (within 4 weeks of baseline), or chronic treatment
- Known hypersensitivity to rabbit proteins
- Hyperlipidemia (fasting LDL cholesterol > 139 mg/dl, treated, or untreated; and/or fasting triglycerides > 200 mg/dl
- Addison's Disease
- Under treatment for a medical condition requiring chronic use of systemic steroids
- Any medical condition that, in the opinion of the investigators, will interfere with the safe completion of the study
- Presence of implanted ferromagnetic devices
- Pregnancy or presently breastfeeding or failure to follow effective contraceptive measures including abstinence (as noted above)
- Active alcohol or substance abuse (as defined above)including cigarettes. Must be abstinent of tobacco for 6 months
- Psychiatric disorder making the subject not suitable for following the protocol
- Presence of implanted ferromagnetic devices
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55455
Yale University School of Medicine
New Haven, Connecticut, 06520
About this study
Official title: The Impact of Pancreatic Islet Cell Allotransplantation on Cognitive Function and Brain Fuel Utilization in Patients With Type 1 Diabetes and Hypoglycemia Unawareness
In patients with Type 1 Diabetes Mellitus, hypoglycemia (low blood sugar) is the rate-limiting step to achieve glucose level control. As a result, understanding the body's responses (including the brain's response) to hypoglycemia is essential for the effective treatment of patients with T1DM. The purpose of this research is to determine whether pancreatic islet cell allotransplantation to restore normoglycemia (normal blood glucose levels) in Type 1 Diabetic patients with hypoglycemia unawareness alters brain fuel utilization and cognitive performance under euglycemic (blood sugar at 100 mg/dl) and hypoglycemic (blood sugar at 50 mg/dl) conditions. Three groups of subjects will be studied: (1) T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected for pancreatic islet cell allotransplantation; (2) T1DM patients who also have a history of severe hypoglycemia and/or hypoglycemia unawareness; (3) nondiabetic subjects. All subjects will undergo identical testing including: (a) screening; (b) neuropsychological testing; (c) and functional magnetic resonance imaging (fMRI) during euglycemic and hypoglycemic conditions.
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes Mellitus, Type 1, Hypoglycemia, Pancreatic Islet Cell Allotransplantation
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected based upon this history to undergo islet cell transplantation at the University of Minnesota. | |
| 2 | T1DM patients (C-peptide negative) who are matched for age, gender, and duration of diabetes, who also have a history of severe hypoglycemia and/or hypoglycemia unawareness meeting the criteria for islet cell transplantation. The hemoglobin A1c for each of these subjects will fall within 1% of the islet transplant recipient to whom they are matched. | |
| 3 | Nondiabetic subjects (fasting plasma glucose < 110 mg/dl) who are matched for age and gender to the islet transplant recipient to whom they are matched. |
What is being measured
The primary outcome is the main question the study is designed to answer.
fMRI
Measured: 0, 3, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2008 (estimated)
- Study startDec 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, Robert Sherwin, Yale University
- Investigators
- Robert Sherwin, M.D., Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590876
- Sponsor's protocol ID
- DK66108a_0304025134
- Other IDs
- R37DK020495, DK20495
- Status last verified
- Oct 2011
- First submitted
- 26 Dec 2007
- Last updated
- 27 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Pancreatic Islet Cell Allotransplantation on Cognitive Function and Brain Fuel Utilization in Patients With Type 1 Diabetes and Hypoglycemia Unawareness
- ClinicalTrials.gov ID
- NCT00590876
- Acronym / sponsor ID
- DK66108a_0304025134
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes Mellitus, Type 1, Hypoglycemia, Pancreatic Islet Cell Allotransplantation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Juvenile Diabetes Research Foundation
- Study start
- Dec 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 11 Jan 2008 (estimated)
- 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.
In patients with Type 1 Diabetes Mellitus, hypoglycemia (low blood sugar) is the rate-limiting step to achieve glucose level control. As a result, understanding the body's responses (including the brain's response) to hypoglycemia is essential for the effective treatment of patients with T1DM. The purpose of this research is to determine whether pancreatic islet cell allotransplantation to restore normoglycemia (normal blood glucose levels) in Type 1 Diabetic patients with hypoglycemia unawareness alters brain fuel utilization and cognitive performance under euglycemic (blood sugar at 100 mg/dl) and hypoglycemic (blood sugar at 50 mg/dl) conditions. Three groups of subjects will be studied: (1) T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected for pancreatic islet cell allotransplantation; (2) T1DM patients who also have a history of severe hypoglycemia and/or hypoglycemia unawareness; (3) nondiabetic subjects. All subjects will undergo identical testing including: (a) screening; (b) neuropsychological testing; (c) and functional magnetic resonance imaging (fMRI) during euglycemic and hypoglycemic conditions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –T1DM patients with a history of severe hypoglycemia and/or hypoglycemia unawareness who have been selected based upon this history to undergo islet cell transplantation at the University of Minnesota. |
| 2 | – | –T1DM patients (C-peptide negative) who are matched for age, gender, and duration of diabetes, who also have a history of severe hypoglycemia and/or hypoglycemia unawareness meeting the criteria for islet cell transplantation. The hemoglobin A1c for each of these subjects will fall within 1% of the islet transplant recipient to whom they are matched. |
| 3 | – | –Nondiabetic subjects (fasting plasma glucose < 110 mg/dl) who are matched for age and gender to the islet transplant recipient to whom they are matched. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Patients undergoing pancreatic islet cell allotransplantation at the University of Minnesota Patients who are seen at Diabetes Clinics at Yale School of Medicine Nondiabetic, healthy subjects from New Haven and surrounding communities
Key inclusion criteria (8 listed)
- T1DM subjects must be 18 years or older and able to provide written consent
- T1DM subjects must be undergoing intensive management, defined by self-monitoring of glucose values 3 or more times each day and by the administration of 3 or more insulin injections each day (or the use of insulin pump therapy). This clinical management must be monitored in close cooperation with an endocrinologist as defined by at least 3 contacts during the previous 12 months.
- T1DM subjects must demonstrate at least one of the following situations that persist despite intensive insulin management efforts:
- metabolic lability/instability, characterized by either 2 or more episodes of severe hypoglycemia within one year (defined as an event with symptoms consistent with hypoglycemia in which the patient requires the assistance of another person, and which is associated with a blood glucose of < 50 mg/dl or prompt recovery after administration of oral carbohydrate, intravenous glucose, or glucagon) or 2 or more hospital admissions for diabetic ketoacidosis over the last year.
- reduced awareness of hypoglycemia (defined by a specific hypoglycemia questionnaire)
Key exclusion criteria (46 listed)
- Age < 18 years
- Body weight > 75 kg at screening
- BMI > 24 (female) and > 25 (male) kg/m2
- Waist to hip ratio greater than or equal to 0.80 (female) and greater than or equal to 0.95 (male)
- Insulin requirement of > 0.7IU/kg/day or > 50 IU per day, whichever is less
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
fMRI
Time frame: 0, 3, and 12 months
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 27 Oct 2011.
Related trials for Diabetes Mellitus, Type 1
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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.
Robert Sherwin, M.D. principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 1, run by Yale University at 2 sites 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 8 inclusion and 46 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 27 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
fMRI (time frame: 0, 3, and 12 months). 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 27 Oct 2011.