Diabetes Type 2Phase 1E2T2DNCT03681691
The Interaction Between Diabetes and Estradiol on Human Brain Metabolism in Postmenopausal Women
A Phase 1 study testing Estradiol patch in people with Diabetes Type 2 and Dementia, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women… Read more about this study
- Who is it for?
- Ages 60 to 80 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Type 2, Dementia
- What is being tested?
- Estradiol patch
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2019to 19 Jul 2021
- Phase
- Phase 1
- 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 60 to 80 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Willing to provide written informed consent
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Female, postmenopausal, aged 60-80
- Normal results on recommended healthcare screenings (e.g., mammogram, pap smear, colonoscopy)
- BMI 20-35 kg/m2
- No evidence of dementia or mild cognitive impairment (MoCA score >25)
- Able to access reliable transportation to study and intervention visits
Who cannot join
- Use of hormone replacement therapy within the past 3 months
- History of renal, heart, liver, or neurological disease; head injury with loss of consciousness in the past 5 years; chronic pain, anxiety or depression
- Presence of medical conditions that might contraindicate estrogen use (e.g., unexplained vaginal bleeding, history of reproductive tissue cancer, thrombosis)
- Currently taking insulin, metformin, or any other drug or medication judged by the study physician to affect safety or research outcomes of interest
- Involved in another research study
- Contraindications for MRI or PET scanning
- Current smoker
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Read the detailed description
Epidemiological studies suggest there may be an interaction between type 2 diabetes and estrogen in postmenopausal women, such that diabetes may interact with estrogen levels over time to increase risk for dementia. The mechanism for this effect is now known. However, animal research suggests that it may occur through estrogen's effects on cellular metabolism of glucose and ketone bodies. The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
- Conditions
- Diabetes Type 2, Dementia
- Being tested
- Estradiol patch
- Keywords
- women's health, estradiol, postmenopausal
- Medical subject headings
- Diabetes Mellitus, Type 2, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol patchDrug
Also called Climara patch
transdermal 17β-estradiol patch
| Study group | Role | What they receive |
|---|---|---|
| Post menopausal women with diabetes | Experimental | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes Receives: Drug: Estradiol patch |
| Post menopausal women without diabetes | Experimental | 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. Receives: Drug: Estradiol patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
Measured: Baseline
FDG PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
Measured: Week 8
Acetoacetate Uptake (AcAc) PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
Measured: Baseline
AcAc PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
Measured: Week 8
Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest.
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use
Measured: Baseline and 8 weeks
Secondary outcomes (14)
Short-Term Memory Composite Score
A composite memory score was created by averaging z-scores for CVLT delayed recall, BVRT delayed recall, and prospective memory. A composite executive function score was created by averaging digit span forwards total correct, digit span backwards total correct, and both verbal fluency scores. Summed z-score ranging from -2 to 2 where higher score indicates better performance.
Measured: Baseline and Week 8
Executive Function Composite Score
The California Verbal Learning Test (CVLT) is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after the short delay (immediately after learning lists) and long delay (25 minutes) are reported. Summed z-score ranging from -2 to 2 where higher score indicates better performance.
Measured: Baseline and Week 8
California Verbal Learning Task (CVLT) Long Delay Free Recall
The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after long delay (25 minutes). The minimum score is 0. The maximum score is 16 and a higher score represents better performance.
Measured: Baseline and Week 8
CVLT Short Delay Free Recall
The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Short delay free recall is immediately after learning lists. The minimum score is 0. The maximum score is 16 and a higher score represents better performance.
Measured: Baseline and Week 8
Benton Visual Retention Task (BVRT) Total Score
The BVRT tests figural memory by testing memory for a line drawing. The minimum score is 0. The scoring used is total correct, the maximum score is 10, and a higher score represents better performance. The total score is reported.
Measured: Baseline and Week 8
Prospective Memory
The Prospective Memory test is a test of everyday memory where participants are given instructions for 3 tasks that will occur later on during the testing session. The minimum score is 0. The maximum score is 12 points, a higher score represents better performance, and the total score is reported
Measured: Baseline and Week 8
Verbal Fluency (Letters)
Participants were given a letter and asked to say aloud as many words as they could think of beginning with that letter. The three letters were F, A, and S, and the participant had one minute per letter to list words. The total score reported is the sum of the correct words generated for all three letters. Although there is no set maximum score, based on published data, it was anticipated that scores could range from 1 to no more than 120. A higher value reflects better performance.
Measured: Baseline and Week 8
Verbal Fluency Score (Fruits and Vegetables)
Participants were given one minute to say aloud as many fruits as possible and one minute to list as many vegetables as possible. The total score reported is the sum of all correct fruits and vegetables listed. Although there is no set maximum score, it was anticipated that scores could range from 0 to no more than 60. A higher value reflects better performance.
Measured: Baseline and Week 8
Digit Span Forward Total Correct
Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in the same order the numbers were presented. The outcome measure reported here is the total number of correct responses (range of scores 0-9). Higher scores reflect better performance.
Measured: Baseline and Week 8
Digit Span Backward Total Correct
Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in reverse order. The outcome measure reported here is the longest span of numbers recalled (range of scores 0-9). Higher scores reflect better performance.
Measured: Baseline and Week 8
Finger Tapping Score--Dominant Hand
The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance.
Measured: Baseline and Week 8
Finger Tapping Score--Non-Dominant Hand
The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the non-dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance.
Measured: Baseline and Week 8
Card Rotations Test Score
The Card Rotations Test is used to assess the ability to mentally rotate figures in space. The test has two parts, each of which last 3 minutes. During each part, the participant is given a sheet of paper with 10 simple geometric figures. Next to each figure is a row of 8 similar figures. Participants are asked to mark whether each of the figures in the row is the same or different than the first figure in the row. The score reported is the number of correct responses. The minimum score is 0. The maximum possible score is 160 and a higher score reflects better performance.
Measured: Baseline and Week 8
Change in Short-term Memory and Executive Function Composite Scores.
A battery of cognitive tasks will be administered before and after estrogen administration. Composite z-scores will be calculated by calculating a z-score for each cognitive task and summing z-scores from -5 (low) to 5 (high) for the tasks designated as short-term memory and executive function.Higher scores denotes better outcomes.
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2018
- Study start13 May 2019
- Primary completion19 Jul 2021
- Study completion19 Jul 2021
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 Diabetes Type 2Studies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Primary Objective: The primary objective is to determine whether the effects of glucose and ketone body uptake to the brain in response to 8-week administration of transdermal 17β-estradiol differ in postmenopausal women with and without type 2 diabetes.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Christina Hugenschmidt, PhD, Principal investigator, Wake Forest Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03681691
- Sponsor's protocol ID
- IRB00049740
- Other IDs
- R21AG054955
- Acronym
- E2T2D
- Status last verified
- Jul 2022
- First submitted
- 10 Sep 2018
- Last updated
- 27 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided at the present time.
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Interaction Between Diabetes and Estradiol on Human Brain Metabolism in Postmenopausal Women
- ClinicalTrials.gov ID
- NCT03681691
- Acronym / sponsor ID
- E2T2D / IRB00049740
- Conditions
- Diabetes Type 2, Dementia
- Keywords
- women's health, estradiol, postmenopausal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 13 May 2019 (actual)
- Primary completion
- 19 Jul 2021 (actual)
- Study completion
- 19 Jul 2021 (actual)
- First posted
- 24 Sep 2018 (actual)
- Results
- Posted 27 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Detailed description
Epidemiological studies suggest there may be an interaction between type 2 diabetes and estrogen in postmenopausal women, such that diabetes may interact with estrogen levels over time to increase risk for dementia. The mechanism for this effect is now known. However, animal research suggests that it may occur through estrogen's effects on cellular metabolism of glucose and ketone bodies. The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Primary Objective: The primary objective is to determine whether the effects of glucose and ketone body uptake to the brain in response to 8-week administration of transdermal 17β-estradiol differ in postmenopausal women with and without type 2 diabetes.
| Arm | Type | Receives |
|---|---|---|
| Post menopausal women with diabetes | Experimental | Drug: Estradiol patch8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes |
| Post menopausal women without diabetes | Experimental | Drug: Estradiol patch8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes. |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Willing to provide written informed consent
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Female, postmenopausal, aged 60-80
- Normal results on recommended healthcare screenings (e.g., mammogram, pap smear, colonoscopy)
- BMI 20-35 kg/m2
Key exclusion criteria (7 listed)
- Use of hormone replacement therapy within the past 3 months
- History of renal, heart, liver, or neurological disease; head injury with loss of consciousness in the past 5 years; chronic pain, anxiety or depression
- Presence of medical conditions that might contraindicate estrogen use (e.g., unexplained vaginal bleeding, history of reproductive tissue cancer, thrombosis)
- Currently taking insulin, metformin, or any other drug or medication judged by the study physician to affect safety or research outcomes of interest
- Involved in another research study
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 |
|---|---|---|
| Estradiol patchAlso: Climara patchtransdermal 17β-estradiol patch | Drug | Post menopausal women with diabetes, Post menopausal women without diabetes |
Primary outcome
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain
Time frame: Baseline
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
FDG PET--Whole Brain
Time frame: Week 8
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
Acetoacetate Uptake (AcAc) PET--Whole Brain
Time frame: Baseline
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
AcAc PET--Whole Brain
Time frame: Week 8
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest.
Time frame: Baseline and 8 weeks
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use
14 secondary outcomes
Short-Term Memory Composite Score
Time frame: Baseline and Week 8
Executive Function Composite Score
Time frame: Baseline and Week 8
California Verbal Learning Task (CVLT) Long Delay Free Recall
Time frame: Baseline and Week 8
CVLT Short Delay Free Recall
Time frame: Baseline and Week 8
Benton Visual Retention Task (BVRT) Total Score
Time frame: Baseline and Week 8
Prospective Memory
Time frame: Baseline and Week 8
Verbal Fluency (Letters)
Time frame: Baseline and Week 8
Verbal Fluency Score (Fruits and Vegetables)
Time frame: Baseline and Week 8
Digit Span Forward Total Correct
Time frame: Baseline and Week 8
Digit Span Backward Total Correct
Time frame: Baseline and Week 8
Finger Tapping Score--Dominant Hand
Time frame: Baseline and Week 8
Finger Tapping Score--Non-Dominant Hand
Time frame: Baseline and Week 8
Card Rotations Test Score
Time frame: Baseline and Week 8
Change in Short-term Memory and Executive Function Composite Scores.
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Undecided at the present time.
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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.
Christina Hugenschmidt, PhD principal investigator
Wake Forest Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Estradiol patch in people with Diabetes Type 2 and Dementia, run by Wake Forest University Health Sciences 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 7 inclusion and 7 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 Sep 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 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?
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain (time frame: Baseline). The study lists 5 primary outcomes in all. 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 Sep 2022.