IMProving Executive Function Study

NCT03187353 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 826981
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Impairment; RRSO

Keywords

Cognitive complaints; RRSO; Oophorectomy; Memory; Cognition; Early menopause

Outcome Measures

Primary Outcomes (1)

• Brown Attention Deficit Disorder Scale (BADDS) Change Score (End of Trial Minus Baseline).

  The Brown Attention Deficit Disorder Scale (BADDS) (Brown, 1996) is a 40-item questionnaire that assesses five subscales of executive functioning. For each item in the questionnaire, participants reported the extent to which it had been a problem over the last six months (0 = never, 1 = once a week or less, 2 = twice a week, or 3 = almost daily). Total BADDS scores can range from 0-120, with higher scores indicating more self-reported difficulties with executive functioning. Outcome measures are reported as change scores for end of trial (6 weeks) minus baseline.

  Outcome measure change score represents end of trial (6 weeks) minus baseline.

Secondary Outcomes (2)

• Brain Activation (Glutamate Contrast)

  6 weeks

• Brain Activation (BOLD Percent Signal Change)

  6 weeks

Study Arms (2)

Lisdexamfetamine, then Placebo

EXPERIMENTAL

Participants will have a 50% chance of first receiving the active study medication. They will begin at 20 mg/d and will increase up to 60 mg/d after 4 weeks, if well tolerated. Total time on the study drug is up to 6 weeks. After a washout period of 2 weeks they will begin with 1 sugar pill and will increase up to 3 pills after 4 weeks. Maximum time for taking the placebo is 6 weeks.

Drug: Lisdexamfetamine; Drug: Placebo oral capsule

Placebo, then Lisdexamfetamine

EXPERIMENTAL

Participants will have a 50% chance of first receiving the placebo, beginning with 1 sugar pill and increasing up to 3 pills after 4 weeks. Maximum time for taking the placebo is 6 weeks. After a washout period of 2 weeks, they will begin active study medication at 20 mg/d and will increase up to 60 mg/d after 4 weeks, if well tolerated. Total time on the study drug is up to 6 weeks.

Drug: Lisdexamfetamine; Drug: Placebo oral capsule

Interventions

Lisdexamfetamine DRUG

Stimulant medications are used to reduce interruptive behavior, fidgeting, and other hyperactive symptoms, as well as help a person finish tasks and improve his or her relationships for adults who have ADHD. Please note that the FDA has not approved the use of Vyvanse® for the treatment of memory and concentration difficulties related to medically induced menopause.

Also known as: Vyvanse

Lisdexamfetamine, then Placebo; Placebo, then Lisdexamfetamine

Placebo oral capsule DRUG

The placebo capsule will be filled with microcellulose.

Also known as: sugar pill

Lisdexamfetamine, then Placebo; Placebo, then Lisdexamfetamine

Eligibility Criteria

• Age: 35 Years - 58 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

3535 Market Street

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• 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.

  PMID: 27550732 BACKGROUND

• 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.

  PMID: 26063677 BACKGROUND

• Brown, T. E. 1996. Brown attention deficit disorder scales for adolescents and adults, San Antonio, TX: The Psychological Corporation.

  RESULT

Related Links

• Research at the Penn Center for Women's Behavioral Wellness

MeSH Terms

Conditions

Cognitive Dysfunction; Primary Ovarian Insufficiency

Interventions

Lisdexamfetamine Dimesylate; Sugars

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; 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; Carbohydrates

Results Point of Contact

• Title: James Loughead, Ph.D.
• Organization: Perlman School of Medicine, University of Pennsylvania

loughead@pennmedicine.upenn.edu

215-205-1876

Study Officials

• C. Neill Epperson, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 14, 2017
• Study Start: September 22, 2017
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Locations

US (1)