Cognitive ImpairmentPhase 4IMPRESNCT03187353

IMProving Executive Function Study

A Phase 4 study testing Lisdexamfetamine in people with Cognitive Impairment and RRSO, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 35 to 58 years, women onlyHealthy volunteers can take part
Conditions the study is for: Cognitive Impairment, RRSO
What is being tested?: Lisdexamfetamine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 69 participants
Where: 1 siteUnited States
Study dates: 22 Sep 2017to 30 Apr 2022
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 35 to 58 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

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);

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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.

Who cannot join

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;

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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).

Trial locations and contacts

1 site in 1 country.

United States1 site

3535 Market Street
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Multi-Modal Imaging of Psychostimulant Effects on Executive Function Post-RRSO

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.

Read the 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.

Conditions: Cognitive Impairment, RRSO
Being tested: Lisdexamfetamine, Placebo oral capsule
Keywords: Cognitive complaints, RRSO, Oophorectomy, Memory, Cognition, Early menopause
Medical subject headings: Cognitive Dysfunction, Primary Ovarian Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LisdexamfetamineDrug
Also called Vyvanse
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.
Placebo oral capsuleDrug
Also called sugar pill
The placebo capsule will be filled with microcellulose.

Study groups in NCT03187353
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Lisdexamfetamine; Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (2)

Brain Activation (Glutamate Contrast)
To measure the effects of Lisdexamfetamine on objective report of executive function difficulties proton magnetic resonance spectroscopy (1H-MRS) was utilized to assess the relative importance of dorsolateral prefrontal cortex (DLPFC) glutamate (Glut) contrast levels during working memory task performance. Measurement of glutamate contrast range from 0 to 15% with higher levels associated with optimal performance. Glutamate contrast is calculated by: GluCEST contrast (%) = [(Msat(-3ppm) - Msat(+3ppm))/Msat(-3ppm)]*100.
Measured: 6 weeks
Brain Activation (BOLD Percent Signal Change)
To measure the effects of Lisdexamfetamine on objective report of executive function difficulties functional magnetic resonance imaging (fMRI) were utilized to assess the relative importance of dorsolateral prefrontal cortex (DLPFC) blood oxygen dependent (BOLD) signals during working memory task performance and the effect of LDX on the executive system activation. Measurement of BOLD perecent signal change range is 0 to 2%. Percent signal change is the difference in fMRI signal between the baseline condition (B) and the task condition (T) and calculated here as: percent signal change = (T-B)/B×100%. Higher percent signal change in the DLPFC is generally associated with better executive function.
Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Sep 201730 Apr 2022

First posted14 Jun 2017
Study start22 Sep 2017
Primary completion30 Apr 2022
Study completion30 Apr 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
More trials run by University of PennsylvaniaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03187353
Sponsor's protocol ID: 826981
Acronym: IMPRES
Status last verified: Oct 2023
First submitted: 12 Jun 2017
Last updated: 18 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

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.
PubMed 27550732
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.
PubMed 26063677
Brown, T. E. 1996. Brown attention deficit disorder scales for adolescents and adults, San Antonio, TX: The Psychological Corporation.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cognitive Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multi-Modal Imaging of Psychostimulant Effects on Executive Function Post-RRSO
ClinicalTrials.gov ID: NCT03187353
Acronym / sponsor ID: IMPRES / 826981
Conditions: Cognitive Impairment, RRSO
Keywords: Cognitive complaints, RRSO, Oophorectomy, Memory, Cognition, Early menopause
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: University of PennsylvaniaUniversity, hospital or other
Study start: 22 Sep 2017 (actual)
Primary completion: 30 Apr 2022 (actual)
Study completion: 30 Apr 2022 (actual)
First posted: 14 Jun 2017 (actual)
Results: Posted 18 Nov 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Lisdexamfetamine, then Placebo	Experimental	Drug: Lisdexamfetamine, Drug: Placebo oral capsuleParticipants 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.
Placebo, then Lisdexamfetamine	Experimental	Drug: Lisdexamfetamine, Drug: Placebo oral capsuleParticipants 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.

Who may qualify

Ages: 35 to 58 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

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;

Key exclusion criteria (14 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LisdexamfetamineAlso: VyvanseStimulant 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.	Drug	Lisdexamfetamine, then Placebo, Placebo, then Lisdexamfetamine
Placebo oral capsuleAlso: sugar pillThe placebo capsule will be filled with microcellulose.	Drug	Lisdexamfetamine, then Placebo, Placebo, then Lisdexamfetamine

Primary outcome

Brown Attention Deficit Disorder Scale (BADDS) Change Score (End of Trial Minus Baseline).
Time frame: Outcome measure change score represents end of trial (6 weeks) 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.

2 secondary outcomes

Brain Activation (Glutamate Contrast)
Time frame: 6 weeks
Brain Activation (BOLD Percent Signal Change)
Time frame: 6 weeks

Results and safety

Results posted to the registry on 18 Nov 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lisdexamfetamine, Then Placebo	36	33
Placebo, Then Lisdexamfetamine	33	30

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

Time frame: Outcome measure change score represents end of trial (6 weeks) minus baseline.. Mean (95% Confidence Interval). Unit: score on a scale

Measure	Lisdexamfetamine (Per Intervention) n = 57	Placebo (Per Intervention) n = 57
Value	-19.68 (-23.17 to -16.18)	-4.31 (-7.84 to -0.78)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lisdexamfetamine, 20 mg	0 of 64 (0%)	2 of 64 (3.1%)	0 of 64
Lisdexamfetamine, 40 mg	0 of 59 (0%)	3 of 59 (5.1%)	0 of 59
Lisdexamfetamine, 60 mg	0 of 43 (0%)	12 of 43 (27.9%)	0 of 43
Placebo	0 of 58 (0%)	4 of 58 (6.9%)	0 of 58

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27550732Shanmugan 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.
Background: PubMed 26063677Epperson 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.
Results publicationBrown, T. E. 1996. Brown attention deficit disorder scales for adolescents and adults, San Antonio, TX: The Psychological Corporation.
Research at the Penn Center for Women's Behavioral WellnessLink provided by the sponsor.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

C. Neill Epperson, MD principal investigator

University of Pennsylvania

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lisdexamfetamine in people with Cognitive Impairment and RRSO, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brown Attention Deficit Disorder Scale (BADDS) Change Score (End of Trial Minus Baseline). (time frame: Outcome measure change score represents end of trial (6 weeks) minus baseline.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03187353, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.