Brain Health and Development With T1DM
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 4 - 16 |
| Updated: | 12/26/2018 |
| Start Date: | September 1, 2016 |
| End Date: | September 2, 2021 |
| Contact: | Samantha Ranck, MSW |
| Email: | rancks@npg.wustl.edu |
| Phone: | 314-362-6514 |
Early Predictors of Brain Health and Development in Youth With T1DM
Type 1 diabetes mellitus (T1DM) is typically diagnosed in childhood and over time can lead to
complications affecting the retina, heart, kidneys, peripheral nerves, and more recently
appreciated, the brain. Studies consistently find that early age of onset and, to a more
variable extent, poor glycemic control over years are associated with reduced cognitive
performance and altered brain structure in children with T1DM. As yet, the investigators'
understanding of why early age of onset would pose more risks for the brain is limited,
making interventions difficult to develop. Given that the initial clinical presentation of
T1DM in children is the earliest and often the most severe glycemic state experienced over
the lifetime, it is possible that age of onset and severity of initial clinical presentation
interact to modify risks for brain health and development. This hypothesis has clear clinical
implications and the potential to resolve conflicting literature, yet has not been explicitly
tested. Thus, the goal of this study is to determine how clinical features at the time of
T1DM diagnosis, such as hyperglycemia, diabetic ketoacidosis (DKA) and degree of beta cell
failure, interact with age of onset to shape the development of the brain and its responses
to subsequent glycemic control.
complications affecting the retina, heart, kidneys, peripheral nerves, and more recently
appreciated, the brain. Studies consistently find that early age of onset and, to a more
variable extent, poor glycemic control over years are associated with reduced cognitive
performance and altered brain structure in children with T1DM. As yet, the investigators'
understanding of why early age of onset would pose more risks for the brain is limited,
making interventions difficult to develop. Given that the initial clinical presentation of
T1DM in children is the earliest and often the most severe glycemic state experienced over
the lifetime, it is possible that age of onset and severity of initial clinical presentation
interact to modify risks for brain health and development. This hypothesis has clear clinical
implications and the potential to resolve conflicting literature, yet has not been explicitly
tested. Thus, the goal of this study is to determine how clinical features at the time of
T1DM diagnosis, such as hyperglycemia, diabetic ketoacidosis (DKA) and degree of beta cell
failure, interact with age of onset to shape the development of the brain and its responses
to subsequent glycemic control.
NewT study staff will work with inpatient diabetes nurses and clinical diabetes educators at
St. Louis Children's Hospital to identify patients that are admitted for new onset T1DM. Once
the patients are clinically stable, the diabetes educator will visit the patient in the
inpatient room and invite the family to participate in the study. If study participants would
like to be enrolled, consent and assent will be obtained at that time. If potential
participants are unsure at that time, the diabetes educator will provide the family with a
blank copy of the consent form to be reviewed. Study information as well as contact
information for study staff so that the family may contact the study should the family have
additional questions or choose to enroll in the study. Following is a description of the
testing days.
Mixed Meal Tolerance Tests (MMTTs) Once the patient has been consented to participate in the
study, in the T1DM group, a Mixed-Meal Tolerance Tests (MMTT) will be administered at both
study visits (3 mo & 21 mo post diagnosis). If participants are in the control group, the
MMTT will only be administered at the 21 mo visit (18 months after the initial visit). For
the MMTT, the T1DM group will be instructed to consume at least 150 g of carbohydrates per
day for 3 days prior to the MMTT and to consume only water after midnight on the night prior
to testing. If the patient is on insulin injection therapy the study nurse will ask the
patient to administer the usual basal insulin dose(s) on the night before or on the morning
of the study but to hold the morning dose of short- and intermediate-acting insulin. If the
patient is on a continuous subcutaneous insulin pump infusions will remain on the usual basal
rates for the duration of the study. For the MMTT a small needle, will be placed to collect
blood samples. While there are multiple collection times, there is only one stick. The study
nurse will then ask participants to drink a Boost High Protein Nutritional Energy Drink.
Blood samples will then be obtained at the following time points: -10, 0, 15, 30, 60, 90,
120, 150, 180, 210, and 240 min. This amounts to approximately 4.5 tablespoons of blood. To
clarify, only the T1DM group will have the MMTT at the first study visit (3 mo after T1DM
dx), both the T1DM and the Control groups will have MMTT at the 21 month visit.
Cognitive Testing The cognitive testing or thinking tests, consist of memory tests, computer
games and vocabulary tests. These tests will be administered by a trained staff member and
will take approximately 60 minutes to complete. Some of the tests are: a Picture Vocabulary
Test, a Picture Sequence Memory Test; an Inhibitory Control and Attention Test; a Dimensional
Change Card Sort Test, and a List Sorting Working Memory Test.
Before and after the cognitive testing, blood glucose levels will be determined (using a
finger prick) for participants in both groups. Participants with blood glucose values below
70 mg/dl or above 300 mg/dl will be treated and re-tested before testing resumes.
At some point during the study, one parent from each family will be requested to perform a
brief reading test that provides an estimated intelligence quotient (IQ). This test takes
approximately 10 minutes.
Interviews Study staff will obtain the parent/guardian's permission to access the patient's
medical records in order to obtain information related to the patient's HbA1c, DKA admissions
and severe hypoglycemic episodes from clinic or hospital visits. In addition, study staff
will interview the proxy regarding these experiences to get additional detail that may not be
captured in the records.
Questionnaires
The proxy will be asked to fill out a study questionnaire either prior to the study visit via
an on-line survey or in person at the study visit. The questionnaire consists of information
related to:
- For parents:
- demographics, education and occupation,
- behavior checklists as it pertains to the participant as well as
- questionnaires asking about the participants' every day activity related to memory
and daily functioning.
- For participants:
- self-report behavioral information as well as
- questionnaires asking about every day activity related to the participants' memory
and daily functioning.
If at any time study participants are uncomfortable completing the questionnaire, are free to
skip any questions that
Magnetic Resonance Imaging (MRI) Participants in both the T1DM and the Control groups will
have an image of the brain at the 3 mo. and the 21 mo visits. An MRI is a non-invasive test
to evaluate the anatomy of the different areas of the brain. A more detailed MRI than the MRI
commonly used in patient care in regular hospitals is planned because we want to make
specialized measurements. This test will take 45-60 minutes. No use of sedation or IV
(through the vein) contrast is planned. The scan involves asking the patient to lie very
still on a small table for 45-60 minutes. After the participant is comfortable on the table
it will then slowly move the participant into the scanner. If the participant would like, a
movie will be available to watch while in the scanner except for a short period of time when
the participant will be asked to stare at a crosshair on the screen.
St. Louis Children's Hospital to identify patients that are admitted for new onset T1DM. Once
the patients are clinically stable, the diabetes educator will visit the patient in the
inpatient room and invite the family to participate in the study. If study participants would
like to be enrolled, consent and assent will be obtained at that time. If potential
participants are unsure at that time, the diabetes educator will provide the family with a
blank copy of the consent form to be reviewed. Study information as well as contact
information for study staff so that the family may contact the study should the family have
additional questions or choose to enroll in the study. Following is a description of the
testing days.
Mixed Meal Tolerance Tests (MMTTs) Once the patient has been consented to participate in the
study, in the T1DM group, a Mixed-Meal Tolerance Tests (MMTT) will be administered at both
study visits (3 mo & 21 mo post diagnosis). If participants are in the control group, the
MMTT will only be administered at the 21 mo visit (18 months after the initial visit). For
the MMTT, the T1DM group will be instructed to consume at least 150 g of carbohydrates per
day for 3 days prior to the MMTT and to consume only water after midnight on the night prior
to testing. If the patient is on insulin injection therapy the study nurse will ask the
patient to administer the usual basal insulin dose(s) on the night before or on the morning
of the study but to hold the morning dose of short- and intermediate-acting insulin. If the
patient is on a continuous subcutaneous insulin pump infusions will remain on the usual basal
rates for the duration of the study. For the MMTT a small needle, will be placed to collect
blood samples. While there are multiple collection times, there is only one stick. The study
nurse will then ask participants to drink a Boost High Protein Nutritional Energy Drink.
Blood samples will then be obtained at the following time points: -10, 0, 15, 30, 60, 90,
120, 150, 180, 210, and 240 min. This amounts to approximately 4.5 tablespoons of blood. To
clarify, only the T1DM group will have the MMTT at the first study visit (3 mo after T1DM
dx), both the T1DM and the Control groups will have MMTT at the 21 month visit.
Cognitive Testing The cognitive testing or thinking tests, consist of memory tests, computer
games and vocabulary tests. These tests will be administered by a trained staff member and
will take approximately 60 minutes to complete. Some of the tests are: a Picture Vocabulary
Test, a Picture Sequence Memory Test; an Inhibitory Control and Attention Test; a Dimensional
Change Card Sort Test, and a List Sorting Working Memory Test.
Before and after the cognitive testing, blood glucose levels will be determined (using a
finger prick) for participants in both groups. Participants with blood glucose values below
70 mg/dl or above 300 mg/dl will be treated and re-tested before testing resumes.
At some point during the study, one parent from each family will be requested to perform a
brief reading test that provides an estimated intelligence quotient (IQ). This test takes
approximately 10 minutes.
Interviews Study staff will obtain the parent/guardian's permission to access the patient's
medical records in order to obtain information related to the patient's HbA1c, DKA admissions
and severe hypoglycemic episodes from clinic or hospital visits. In addition, study staff
will interview the proxy regarding these experiences to get additional detail that may not be
captured in the records.
Questionnaires
The proxy will be asked to fill out a study questionnaire either prior to the study visit via
an on-line survey or in person at the study visit. The questionnaire consists of information
related to:
- For parents:
- demographics, education and occupation,
- behavior checklists as it pertains to the participant as well as
- questionnaires asking about the participants' every day activity related to memory
and daily functioning.
- For participants:
- self-report behavioral information as well as
- questionnaires asking about every day activity related to the participants' memory
and daily functioning.
If at any time study participants are uncomfortable completing the questionnaire, are free to
skip any questions that
Magnetic Resonance Imaging (MRI) Participants in both the T1DM and the Control groups will
have an image of the brain at the 3 mo. and the 21 mo visits. An MRI is a non-invasive test
to evaluate the anatomy of the different areas of the brain. A more detailed MRI than the MRI
commonly used in patient care in regular hospitals is planned because we want to make
specialized measurements. This test will take 45-60 minutes. No use of sedation or IV
(through the vein) contrast is planned. The scan involves asking the patient to lie very
still on a small table for 45-60 minutes. After the participant is comfortable on the table
it will then slowly move the participant into the scanner. If the participant would like, a
movie will be available to watch while in the scanner except for a short period of time when
the participant will be asked to stare at a crosshair on the screen.
T1DM Group
Inclusion Criteria:
- Otherwise healthy children with T1DM
- Between the ages of 4 to 16 years old
- Must be able to lie still in the MRI for 60 minutes
Exclusion Criteria:
- Mental retardation
- Enrollment in special education classes or receiving special services
- Major psychiatric (e.g. depression, autism) or neurological illnesses (e.g. head
injury with loss of consciousness)
- Currently taking medications with known central nervous system effects (including
those for ADHD)
- Physical limitations that would interfere with testing
- Contraindications for MRI scans
- Females who are pregnant and/or lactating will be excluded
- Chronic diseases in addition to T1DM other than well-controlled asthma, celiac disease
or Hashimoto's thyroiditis as determined by their clinical endocrinologist and/or
nurse
Sibling Control Group
Inclusion Criteria:
- Healthy sibling of a T1DM participant
- Matched with a T1DM participant for age and gender
- Between the ages of 4 to16 years old
- Must be able to lie still in the MRI for 60 minutes
Exclusion Criteria
- Mental retardation
- Enrollment in special education classes or receiving special services
- Major psychiatric (e.g. depression, autism) or neurological illnesses (e.g. head
injury with loss of consciousness)
- Currently taking medications with known central nervous system effects (including
those for ADHD)
- Physical limitations that would interfere with testing
- Contraindications for MRI scans
- Females who are pregnant and/or lactating will be excluded
- Chronic diseases other than well-controlled asthma, celiac disease or Hashimoto's
thyroiditis as determined by their clinical endocrinologist and/or nurse.
The Parent population will consist of one biological parent for each minor participant. The
proxy participant will complete two neuropsychological tests as well as answer
questionnaires about the minor study participant. The parent population has no age
limitations but must be a biological parent to the minor study participant. The testing
takes approximately 20 minutes thus the parent population will not be paid for their
participation.
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Tamara G Hershey, PhD
Phone: 314-362-6514
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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