Clinical trial NCT03681691: The Interaction Between Diabetes and Estradiol on Human Brain Metabolism in Postmenopausal Women
Official title: The Interaction Between Diabetes and Estradiol on Human Brain Metabolism in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes Type 2
Dementia
Keywords: women's health
estradiol
postmenopausal
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-09-24
Enrollment: 12
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: OTHER

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. Willing to provide written informed consent
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Female, postmenopausal, aged 60-80
4. Normal results on recommended healthcare screenings (e.g., mammogram, pap smear, colonoscopy)
5. BMI 20-35 kg/m2
6. No evidence of dementia or mild cognitive impairment (MoCA score \>25)
7. Able to access reliable transportation to study and intervention visits

Exclusion Criteria:

1. Use of hormone replacement therapy within the past 3 months
2. History of renal, heart, liver, or neurological disease; head injury with loss of consciousness in the past 5 years; chronic pain, anxiety or depression
3. Presence of medical conditions that might contraindicate estrogen use (e.g., unexplained vaginal bleeding, history of reproductive tissue cancer, thrombosis)
4. Currently taking insulin, metformin, or any other drug or medication judged by the study physician to affect safety or research outcomes of interest
5. Involved in another research study
6. Contraindications for MRI or PET scanning
7. Current smoker

Primary outcomes:
measure: Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain
timeFrame: Baseline
measure: FDG PET--Whole Brain
timeFrame: Week 8
measure: Acetoacetate Uptake (AcAc) PET--Whole Brain
timeFrame: Baseline
measure: AcAc PET--Whole Brain
timeFrame: Week 8
measure: Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest.
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Short-Term Memory Composite Score
timeFrame: Baseline and Week 8
measure: Executive Function Composite Score
timeFrame: Baseline and Week 8
measure: California Verbal Learning Task (CVLT) Long Delay Free Recall
timeFrame: Baseline and Week 8
measure: CVLT Short Delay Free Recall
timeFrame: Baseline and Week 8
measure: Benton Visual Retention Task (BVRT) Total Score
timeFrame: Baseline and Week 8
measure: Prospective Memory
timeFrame: Baseline and Week 8
measure: Verbal Fluency (Letters)
timeFrame: Baseline and Week 8
measure: Verbal Fluency Score (Fruits and Vegetables)
timeFrame: Baseline and Week 8
measure: Digit Span Forward Total Correct
timeFrame: Baseline and Week 8
measure: Digit Span Backward Total Correct
timeFrame: Baseline and Week 8
measure: Finger Tapping Score--Dominant Hand
timeFrame: Baseline and Week 8
measure: Finger Tapping Score--Non-Dominant Hand
timeFrame: Baseline and Week 8
measure: Card Rotations Test Score
timeFrame: Baseline and Week 8
measure: Change in Short-term Memory and Executive Function Composite Scores.
timeFrame: Baseline and 8 weeks
Other outcomes:
measure: Regional Ratio of Ketone/Glucose Uptake
timeFrame: Baseline and Week 8
measure: Number of White Matter Hypertensities
timeFrame: Baseline and Week 8
measure: Number of Microbleeds
timeFrame: Baseline and Week 8
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest Health Sciences
name: Christina Hugenschmidt, PhD
role: PRINCIPAL_INVESTIGATOR
References: