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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| C. Neill Epperson, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 3535 Market Street | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27550732 | Background | 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. | |
| 26063677 |
| Label | URL |
|---|---|
| Research at the Penn Center for Women's Behavioral Wellness | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lisdexamfetamine, Then Placebo | 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. |
| FG001 | Placebo, Then Lisdexamfetamine | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (6 Weeks) |
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| Washout (2 Weeks) |
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| Second Intervention (6 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lisdexamfetamine, Then Placebo | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Outcome measure change score represents end of trial (6 weeks) minus baseline. |
|
6 months
We collected and reported all untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lisdexamfetamine, 20 mg | Reporting AEs experienced for all participants who were exposed to Lisdexamfetamine at 20 mg. In total, 64 participants were exposed to 20mg of the drug (all participants who were exposed to LDX are included in this grouping). All AEs reported while on the 20mg dose are listed below. During active study participation, Participants had a 50% chance of receiving the active study medication during trial A. They began at 20 mg/d and increased up to 40 mg after 1 week and then up to 60 mg/d after 4 weeks, if well tolerated. Total time on the study drug is up to 6 weeks. Lisdexamfetamine: 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Change in Appetite | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| James Loughead, Ph.D. | Perlman School of Medicine, University of Pennsylvania | 215-205-1876 | loughead@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 11, 2020 | May 1, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D016649 | Primary Ovarian Insufficiency |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D010049 | Ovarian Diseases |
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| ID | Term |
|---|---|
| D000069478 | Lisdexamfetamine Dimesylate |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D003913 | Dextroamphetamine |
| D000661 | Amphetamine |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
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|
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| Placebo oral capsule | Drug | The placebo capsule will be filled with microcellulose. |
|
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| 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. | 6 weeks |
| 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. |
| Result | Brown, T. E. 1996. Brown attention deficit disorder scales for adolescents and adults, San Antonio, TX: The Psychological Corporation. |
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| NOT COMPLETED |
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| BG001 | Placebo, Then Lisdexamfetamine | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Placebo (Per Intervention) | Participants who received placebo (1 sugar pill and will increase up to 3 pills after 4 weeks) in either the first 6 weeks or last six weeks of the study. |
|
|
| Secondary | 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. | In response to the COVID -19 pandemic baseline neuroimaging data was only collected and analyzed on a subset of study participant (n=14). | Posted | Mean | Standard Deviation | percentage of Glutmate Contrast | 6 weeks |
|
|
|
| Secondary | 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. | In response to the COVID -19 pandemic baseline neuroimaging data was only collected and analyzed on a subset of study participant (n=14). | Posted | Mean | Standard Deviation | percentage of signal change | 6 weeks |
|
|
|
| 0 |
| 64 |
| 0 |
| 64 |
| 2 |
| 64 |
| EG001 | Lisdexamfetamine, 40 mg | Reporting AEs experienced for all participants who were exposed to Lisdexamfetamine at 40 mg. In total, 59 participants were exposed to 40mg of the drug (5 people remained on 20mg for the duration of their trial and are not included in the 40mg or 60mg groupings). All AEs reported while on the 40mg dose are listed below. During active study participation, Participants had a 50% chance of receiving the active study medication during trial A. They began at 20 mg/d and increased up to 40 mg after 1 week and then up to 60 mg/d after 4 weeks, if well tolerated. Total time on the study drug is up to 6 weeks. Lisdexamfetamine: 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. | 0 | 59 | 0 | 59 | 3 | 59 |
| EG002 | Lisdexamfetamine, 60 mg | Reporting AEs experienced for all participants who were exposed to Lisdexamfetamine at 60 mg. In total, 43 participants were exposed to 60mg of the drug (16 people remained at 40mg, but did not increase to 60mg and therefore are not included in this 60mg grouping). All AEs reported while on the 60mg dose are listed below. During active study participation, Participants had a 50% chance of receiving the active study medication during trial A. They began at 20 mg/d and increased up to 40 mg after 1 week and then up to 60 mg/d after 4 weeks, if well tolerated. Total time on the study drug is up to 6 weeks. Lisdexamfetamine: 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. | 0 | 43 | 0 | 43 | 12 | 43 |
| EG003 | Placebo | Reporting AEs experienced for all participants who were exposed to placebo capsules. In total, 58 participants were exposed to the placebo. All AEs reported while on placebo are listed below. Participants will have a 50% chance of receiving the placebo for this study. 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 oral capsule: The placebo capsule will be filled with microcellulose. | 0 | 58 | 0 | 58 | 4 | 58 |
| Difficulty falling or staying asleep | General disorders | Non-systematic Assessment |
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| Dizziness/Disorientation | Nervous system disorders | Non-systematic Assessment |
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| Dry Mouth | General disorders | Non-systematic Assessment |
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| mild to moderate headache | Nervous system disorders | Non-systematic Assessment | mild to moderate headache |
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| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Increased blood pressure | Cardiac disorders | Non-systematic Assessment | Blood pressure increased above normal reading |
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| Drowsiness | Nervous system disorders | Non-systematic Assessment |
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| Diarrhea/Gas | Gastrointestinal disorders | Non-systematic Assessment |
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| Jitters | Nervous system disorders | Non-systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Soreness/Tingling Skin | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Increased Thirst | General disorders | Non-systematic Assessment |
|
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| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D005021 |
| Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D002241 | Carbohydrates |