Clinical trial NCT03187353: IMProving Executive Function Study
Official title: Multi-Modal Imaging of Psychostimulant Effects on Executive Function Post-RRSO
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cognitive Impairment
RRSO
Keywords: Cognitive complaints
RRSO
Oophorectomy
Memory
Cognition
Early menopause
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2017-06-14
Enrollment: 69
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a double-blind, placebo-controlled, crossover study testing whether Vyvanse (lisdexamfetamine; LDX) improves executive functioning (EF) in 100 postmenopausal women who report onset of EF difficulties after oophorectomy. This study involves magnetic resonance imaging (MRI) to see how LDX affects brain chemistry while undergoing two 6-week trials of the study drug and placebo capsules.

UPDATE: We have recently updated this protocol (09/2020) to offer a remote version of the study that can be completed entirely from the participant's home. This alternate version of the study eliminates travel, the MRI, and blood draws.

Detailed description: Following a medically induced menopause, many women report difficulty in remembering things, focusing and concentrating. The purpose of this study is to examine the effects of a stimulant medication called Vyvanse® (lisdexamfetamine; LDX) on executive functioning, such as attention, processing, organization, and memory, in women who are experiencing executive functioning difficulties after having undergone a risk-reducing bilateral salpingo-oophorectomy (RRSO). This study involves magnetic resonance imaging (MRI) to see how LDX affects brain chemistry while undergoing two 6-week trials of the study drug and placebo capsules.

Individuals wishing to participate in this study are medically healthy women between the ages of 35-58 years old who have undergone a risk-reducing bilateral salpingo-oophorectomy (RRSO) within the previous 15 years. Participants must have been premenopausal before undergoing RRSO (meaning they were having regular periods). They also must not have undergone radiation or chemotherapy in the past year.

Furthermore, participants must not suffer from a mental illness, including Attention Deficit Hyperactivity Disorder (ADHD), and must not have a recent history of drug abuse. Additionally, participants must not suffer from a fear of small, enclosed spaces (claustrophobia), and not have any implanted medical devices such as a pacemaker, orthodontic braces, or shrapnel. They must not have a history of seizures, uncontrolled hypertension or known renal impairment.

Eligibility criteria: Inclusion Criteria:

* Female;
* Age 35-58;
* Have undergone risk-reducing bilateral salpingo-oophorectomy (RRSO) within the previous 15 years AND were premenopausal at the time of RRSO;
* Score of ≥ 20 on the Brown Attention Deficit Disorder Scale (BADDS);
* Onset of executive function difficulties occurred post RRSO;
* Clean urine drug screen (nicotine and marijuana are permissible);
* Are fluent in written and spoken English;
* Are able to give written informed consent (obtained at screening visit);
* Have a high school diploma or equivalent degree (i.e., GED), as per subject report;
* If using aromatase inhibitors or tamoxifen: Must have been on a stable dose for at least 6 months;
* If completing visits remotely: Must have access to a telecommunications application (i.e., Skype), email, scanner/fax machine, and a private area that enables the protection of participant confidentiality.

Exclusion criteria:

* Current, untreated psychiatric disorder;
* Substance use disorder within the previous 3 years;
* Lifetime history of ADHD or psychotic disorder including bipolar disorder, schizoaffective disorder, and schizophrenia;
* Lifetime history of stimulant abuse or dependence;
* Regular use of psychotropic medications except selective serotonin reuptake inhibitors (SSRI), serotonin noradrenergic reuptake inhibitors (SNRI), bupropion, zolpidem, gabapentin, or buspirone;
* Chemotherapy within the past year;
* Previous history of sensitivity or adverse reaction to lisdexamfetamine (LDX);
* History of seizures or unstable medical condition;
* Known heart disease or clinically significant abnormal electrocardiogram during screening as determined by the study MD;
* Uncontrolled hypertension;
* Presence of a metallic implant contraindicative to scanning at the 7T level;
* Claustrophobia.
* Consistent systolic blood pressure of \>145mm Hg or diastolic blood pressure \>90 mm Hg after three readings at time of screening;
* Known renal impairment and End Stage Renal Disease (ESRD).

Primary outcomes:
measure: Brown Attention Deficit Disorder Scale (BADDS) Change Score (End of Trial Minus Baseline).
timeFrame: Outcome measure change score represents end of trial (6 weeks) minus baseline.
Secondary outcomes:
measure: Brain Activation (Glutamate Contrast)
timeFrame: 6 weeks
measure: Brain Activation (BOLD Percent Signal Change)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: 3535 Market Street
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: C. Neill Epperson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shanmugan S, Loughead J, Nanga RP, Elliott M, Hariharan H, Appleby D, Kim D, Ruparel K, Reddy R, Brown TE, Epperson CN. Lisdexamfetamine Effects on Executive Activation and Neurochemistry in Menopausal Women with Executive Function Difficulties. Neuropsychopharmacology. 2017 Jan;42(2):437-445. doi: 10.1038/npp.2016.162. Epub 2016 Aug 23.
citation: Epperson CN, Shanmugan S, Kim DR, Mathews S, Czarkowski KA, Bradley J, Appleby DH, Iannelli C, Sammel MD, Brown TE. New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology (Berl). 2015 Aug;232(16):3091-100. doi: 10.1007/s00213-015-3953-7. Epub 2015 Jun 11.
citation: Brown, T. E. 1996. Brown attention deficit disorder scales for adolescents and adults, San Antonio, TX: The Psychological Corporation.