E2 and LDX for the Treatment of Cognitive Complaints After Oophorectomy

NCT01986764 | Withdrawn

• 1 other identifier: 817642
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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®).

Conditions

Planned RRSO

Keywords

oophorectomy; RRSO; menopause; early menopause; cognition; memory; brain-imaging

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Cognitive Functioning

  12 weeks

Study Arms (3)

lisdexamfetamine

ACTIVE COMPARATOR

lisdexamfetamine 20 mg/d to 60 mg/d for 12 weeks

Drug: Lisdexamfetamine

Estradiol

ACTIVE COMPARATOR

Estradiol 1 mg/d to 3 mg/d for 12 weeks

Drug: Estradiol

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Lisdexamfetamine DRUG

Also known as: Vyvanse

lisdexamfetamine

Estradiol DRUG

Also known as: Estrogen

Estradiol

Placebo DRUG

Placebo capsules will be filled with lactose powder.

Placebo

Eligibility Criteria

• Age: 30 Years - 48 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women ages 30 to 48 will be eligible for this study if they:
• 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;
• Planning to undergo an oophorectomy or full hysterectomy;
• Are premenopaual (have a baseline follicle stimulating hormone level (FSH) of \<20 IU/ml);
• Smoke \< 10 cigarettes per day
• Are right-handed;
• Can provide proof of having had a gynecological exam and PAP test done within the previous 3 years at the time of screening;
• Can provide proof of having had a mammogram within the previous 12 months at the time of screening;
• Are able to give written informed consent;
• Must have clear urine toxicology screen upon recruitment;
• Are fluent in written and spoken English;
• Negative urine pregnancy test.

You may not qualify if:

• Mini-mental status exam score of less than or equal to 24;
• 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;
• Lifetime history of drug addiction or abuse, excepting nicotine;
• Regular use of other psychotropic medication;
• Regular use (more than once a week) of alcohol that is greater than 3 drinks per day;
• 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;
• History of seizures;
• 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;
• Claustrophobia;
• History of cardiac disease including known cardiac defect or conduction abnormality;
• Abnormal electrocardiogram during screening;
• Current pregnancy or planning to become pregnant;
• Presence of a metallic implant

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Penn Center for Women's Behavioral Wellness

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Interventions

Lisdexamfetamine Dimesylate; Estradiol; Estrogens

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• C. Neill Epperson, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 18, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: March 24, 2017

Record last verified: 2017-03

Locations

US (1)