Early Menopause Hormone Treatment and Cognition (R21)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yolanda Smith, M.D., University of Michigan
ClinicalTrials.gov Identifier:
NCT01046643
First received: January 11, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The objective of this study is to evaluate the neurobiological effects of hormone therapy (HT) in healthy early postmenopausal women. The studies proposed in this project seek to define the association between different hormone forms (estradiol only and progesterone only) versus placebo on brain functional measures. The functional measures will include the performance of the volunteers on a comprehensive neuropsychological testing battery, and the brain functional responses to episodic memory (verbal and non-verbal) challenges as well as emotional processing determined with functional magnetic resonance imaging (fMRI).


Condition Intervention
Menopausal Syndrome
Drug: Estradiol (E2)
Drug: Progesterone (P10) x90
Drug: Progesterone (P10) x10

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Hormones and Cognitive Processing in Early Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans [ Time Frame: August 2010 - March 2012 ] [ Designated as safety issue: No ]

    Measure the changes in brain activity in verbal tasks with hormone use (either estradiol or progesterone) versus placebo.

    The test is a deep and shallow verbal processing task, where the subjects are presented lists of words, one word at a time, and are asked to make one of 2 decisions about each list. One decision is whether each word is written in upper or lower case letters (shallow processing), and the other decision is whether each word denotes an abstract or concrete concept (deep processing).

    The test was administered 3 months after baseline and 38 weeks after baseline.


  • Changes in Brain Activation Patterns in Visual Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans [ Time Frame: August 2010 - March 2012 ] [ Designated as safety issue: No ]

    Measure the changes in brain activity in visual tasks with hormone use (either estradiol or progesterone) versus placebo.

    The test is a visual working memory task, where the women are presented with 3 geometric grids on the screen. The target grid is on top, and 2 test grids are on the bottom. The women must decide if the right or left test grid matches the grid on top. There are 3 conditions: a match condition where all 3 grids are shown simultaneously, and 2 delay conditions, where the target grid is shown first, disappears, and the test grids appear after a 1 or a 4 second delay.

    The test was administered 3 months after baseline and 38 weeks after baseline.



Secondary Outcome Measures:
  • Neuropsychological Testing Scores - Verbal Learning Retention [ Time Frame: August 2010 - March 2012 ] [ Designated as safety issue: No ]

    Changes in neuropsychological testing measures (verbal learning retention) with hormone use (either estradiol or progesterone) versus placebo.

    Subjects are given tests that present them with a series of words. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the Benton Visual Memory Test, Revised.

    The tests were administered 3 months after baseline and 38 weeks after baseline.


  • Neuropsychological Testing Scores - Visual Learning Retention [ Time Frame: August 2010 - March 2012 ] [ Designated as safety issue: No ]

    Changes in neuropsychological testing measures (visual learning retention) with hormone use (either estradiol or progesterone) versus placebo.

    Subjects are given tests that present them with a series of pictures. They are asked to recall how many items they can remember, and then some time later, are asked to recall the items again. The retention measure is how many items they can remember at the later time point, compared to the earlier time point. Adapted from the California Verbal Learning Test - 2nd edition.

    The tests were administered 3 months after baseline and 38 weeks after baseline.



Enrollment: 30
Study Start Date: May 2010
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Estrogen followed by Placebo
Estrogen treatment with Estradiol (E2) followed by Placebo.
Drug: Estradiol (E2)
One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days; followed by one Progesterone (200mg) once a day, at the same time each day, for 10 days to slough endometrial lining; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Other Name: E2
Drug: Progesterone (P10) x10
One Progesterone (200mg) capsule once a day for 10 days, to slough endometrial lining for patients taking Estradiol. Patients taking Progesterone will take an equivalent Placebo capsule during this time period.
Other Name: P10
Active Comparator: Progesterone followed by Placebo
Progesterone (P10) treatment followed by Placebo.
Drug: Progesterone (P10) x90
One Progesterone capsule (200mg) once a day, at the same time each day, for 90 days; followed by one Placebo capsule (to mirror Progesterone capsule to slough endometrial lining in Estradiol recipients) once a day, at the same time each day, for 10 days ; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Other Name: P10
Active Comparator: Placebo followed by Estrogen
Placebo followed by Estrogen treatment with Estradiol (E2)
Drug: Estradiol (E2)
One Estradiol capsule (1mg) once a day, at the same time each day, for 90 days; followed by one Progesterone (200mg) once a day, at the same time each day, for 10 days to slough endometrial lining; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Other Name: E2
Drug: Progesterone (P10) x10
One Progesterone (200mg) capsule once a day for 10 days, to slough endometrial lining for patients taking Estradiol. Patients taking Progesterone will take an equivalent Placebo capsule during this time period.
Other Name: P10
Active Comparator: Placebo followed by Progesterone
Placebo followed by Progesterone (P10) treatment.
Drug: Progesterone (P10) x90
One Progesterone capsule (200mg) once a day, at the same time each day, for 90 days; followed by one Placebo capsule (to mirror Progesterone capsule to slough endometrial lining in Estradiol recipients) once a day, at the same time each day, for 10 days ; followed by one Placebo capsule once a day, at the same time each day, for 90 days.
Other Name: P10

Detailed Description:

Specific Aims

Aim 1. To examine the effects of estradiol alone on brain functioning in early post-menopausal women during verbal and non-verbal cognitive tasks.

Hypothesis: It is expected that with estradiol treatment brain activation will be more prominent in the hippocampus and prefrontal cortical areas compared to placebo. The magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.

Aim 2. To determine the effects of progesterone alone on brain functioning in early postmenopausal women during verbal and non-verbal cognitive tasks.

Hypothesis: It is expected that with progesterone treatment brain activation in the hippocampus and prefrontal cortical areas will be decreased compared to both the placebo condition (within subjects) and the estradiol condition (between subjects). Interindividual variations in the magnitude of activation in these regions will be positively correlated with task performance in the scanner and with the results of neuropsychological tests assessing verbal and non-verbal delayed recall.

Aim 3. To determine the individual effects of estradiol and progesterone on brain functioning in early postmenopausal women during emotional processing stimuli.

Hypothesis: During negative stimuli estradiol-treated women compared to placebo group, are expected to have increased activity in the amygdala, posterior cingulate, and orbitofrontal cortex, while in progesterone-treated women compared to placebo, decreased activity is expected in these brain regions.

  Eligibility

Ages Eligible for Study:   45 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal women
  • Ages 45-55, 6 - 36 months from their last menstrual period.

Exclusion Criteria:

  • Left handedness
  • Acute medical illness
  • Neurologic illness
  • Psychiatric illness
  • Heart disease
  • Thromboembolic disease
  • Liver disease
  • Uncorrected thyroid disease
  • Diabetes
  • Neurological disease
  • Porphyria
  • Allergy to estradiol
  • Progesterone or lactose
  • Lactose intolerance
  • Claustrophobia
  • Contraindications to MRI (including pacemakers, surgical clips or metallic surgical devices)
  • Smoking within the last 3 years
  • Use of hormones within the last 3 months
  • Current or past history of substance abuse
  • History of head injury or loss of consciousness
  • Medications with actions on the central nervous system
  • Endometrial lining greater than 5mm
  • Ovarian pathology on ultrasound
  • Abnormal mammogram
  • Migraines
  • Fasting cholesterol >300 mg/dl, and fasting triglycerides >300 mg/dl
  • Creatinine level > 1.5 mg/dl
  • Aspartate transaminase (AST) or Alanine transaminase (ALT) greater than two times the top normal range
  • Follicle stimulating hormone (FSH) values <40 IU/L
  • estradiol >40 pg/ml.
  • Subjects with HAM-D score > 8, HAM-A > 6 during screening will not be eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01046643

Locations
United States, Michigan
The University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Yolanda R. Smith, M.D. University of Michigan
  More Information

No publications provided

Responsible Party: Yolanda Smith, M.D., Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01046643     History of Changes
Other Study ID Numbers: 1R21AG031951 - 01A1, 1R21AG031951-01A1
Study First Received: January 11, 2010
Results First Received: February 2, 2013
Last Updated: May 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Women
Healthy
Menopausal
Hormone treatment

Additional relevant MeSH terms:
Hormones
Progesterone
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on September 30, 2014