E2 and LDX for the Treatment of Cognitive Complaints After Oophorectomy (E2LDX)

Predictors of Healthy Mood and Memory After Oophorectomy

This project seeks to address cognitive disturbance, which is a frequent adverse sequelae of riskreducing bilateral salpingo-oophorectomy (RRSO) with or without post-procedure chemotherapy and adjunctive treatments. RRSO after completion of childbearing is recommended for prevention of ovarian and breast cancer in women with BRCA1/BRCA2 mutations and standard of care for women with some forms of hormone-responsive cancer. Knowledge regarding the impact of this procedure, with or without chemotherapy, and subsequent hypogonadism on brain health is less than adequate. Premenopausal women who undergo an acute surgical menopause are at greater risk for verbal memory decline and executive function (EF) complaints, but as of yet, we cannot predict who is going to experience these adverse sequelae, nor do we have targeted prevention or treatment strategies other than hormone therapy, which is not an option in many cases and not always effective. An idealized sample as women who are planning for a RRSO will undergo brain imaging and behavioral assessments pre- and post-surgery as well as pre-/post-treatment with E2 or the psychostimulant, lisdexamphetamine (LDX; Vyvanse®).

Study Overview

• Status: Withdrawn
• Conditions: Planned RRSO
• Intervention / Treatment: Drug: Estradiol; Drug: Lisdexamfetamine; Drug: Placebo

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Center for Women's Behavioral Wellness

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 48 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Women ages 30 to 48 will be eligible for this study if they:

1. Have no previous or present history of a DSM-IV psychiatric disorder within the previous year or substance dependence disorder within the previous 5 years (psychostimulant abuse lifetime history), according to the Structured Clinical Interview for Diagnosis- DSM-IV (SCID)-Non-Patient Version;
2. Planning to undergo an oophorectomy or full hysterectomy;
3. Are premenopaual (have a baseline follicle stimulating hormone level (FSH) of <20 IU/ml);
4. Smoke < 10 cigarettes per day
5. Are right-handed;
6. Can provide proof of having had a gynecological exam and PAP test done within the previous 3 years at the time of screening;
7. Can provide proof of having had a mammogram within the previous 12 months at the time of screening;
8. Are able to give written informed consent;
9. Must have clear urine toxicology screen upon recruitment;
10. Are fluent in written and spoken English;
11. Negative urine pregnancy test.

Exclusion Criteria:

1. Mini-mental status exam score of less than or equal to 24;
2. Presence of a psychiatric disorder within previous year or a life time history of ADHD or psychotic disorder including bipolar disorder, schizoaffective disorder and schizophrenia;
3. Lifetime history of drug addiction or abuse, excepting nicotine;
4. Regular use of other psychotropic medication;
5. Regular use (more than once a week) of alcohol that is greater than 3 drinks per day;
6. Presence of a contraindication to treatment with stimulant medication; this would include the presence of hypertension (controlled or uncontrolled), coronary disease, atrial fibrillation, and arrhythmia;
7. History of seizures;
8. Presence of a contraindication to treatment with estrogen; this would include the presence of a history of blood clots, and estrogen-receptor positive breast cancer;
9. Claustrophobia;
10. History of cardiac disease including known cardiac defect or conduction abnormality;
11. Abnormal electrocardiogram during screening;
12. Current pregnancy or planning to become pregnant;
13. Presence of a metallic implant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo capsules will be filled with lactose powder.
ACTIVE_COMPARATOR: lisdexamfetamine; lisdexamfetamine 20 mg/d to 60 mg/d for 12 weeks	Drug: Lisdexamfetamine; Other Names: Vyvanse
ACTIVE_COMPARATOR: Estradiol; Estradiol 1 mg/d to 3 mg/d for 12 weeks	Drug: Estradiol; Other Names: Estrogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BADDS Score	This study uses a double-blind, placebo-controlled, design. The primary subjective outcome variable is the BADDS score measured at the initial screening visit, and one week after oophorectomy and 12 weeks after randomization to E2, LDX or placebo post-oophorectomy. The primary, out-of-scan objective outcome will be performance on the HVLT, while the primary, in-scanner outcomes will be behavioral and brain activation measures during performance of the N-back task.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Functioning	The secondary outcome variable studies changes in memory assessed using a battery of cognitive tasks.	12 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2013
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: October 30, 2013
• First Submitted That Met QC Criteria: November 11, 2013
• First Posted (ESTIMATE): November 18, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 24, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: memory; menopause; cognition; oophorectomy; early menopause; RRSO; brain-imaging
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Estradiol; Lisdexamfetamine Dimesylate; Estrogens
• Other Study ID Numbers: 817642