Cognitive ImpairmentPhase 4NCT02595723
Phenytoin for Memory Impairment Secondary to Megestrol
A Phase 4 study testing Phenytoin 200 mg capsule and Megestrol 800 mg liquid in people with Cognitive Impairment, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
This study is designed to test if megestrol acetate induces changes in declarative memory in healthy controls and if pre-administration of phenytoin can ameliorate any induced cognitive impairments. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Impairment
- What is being tested?
- Phenytoin 200 mg capsule and Megestrol 800 mg liquid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Dec 2016
- 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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women age 18-50 years
- Education of ≥ 12 years and baseline Rey Auditory Verbal Learning Test (RAVLT) total words recalled score ≥ 40 (normal baseline memory)
- Body mass index (BMI) between 18.5-35
- The ability to read and speak English as not all neurocognitive assessments have been translated and validated in other languages.
Who cannot join
- History (lifetime) of Bipolar Disorder, Major Depressive Disorder, psychotic depressive, schizophrenic, schizoaffective, or other Axis I psychotic disorders
- Has an unstable general medical condition (GMC) or significant medical condition, including but not limited to myocardial infarction, cancer, diabetes (hypertension is allowed if condition is being treated and is stable)
- Vulnerable populations including pregnant or nursing women, the incarcerated, or those with severe cognitive disorders
- Education history that includes Special Education or history of mental disability
- History of psychotropic medication therapy in the past 30 days
- Baseline Quick Inventory of Depressive Symptoms-Clinician Rated (QIDS-C) > 5
Show all 17Show fewer
- Initiation of new medications within 14 days of the baseline visit, with the exception of over-the-counter (OTC) as needed medications (e.g. Tylenol, Advil, Motrin, etc.)
- Significant hypertensive blood pressure at baseline, defined as either systolic pressure > 150 or diastolic pressure > 95
- Febrile at baseline, defined as body temperature ≥ 100.5°F (38°C)
- Baseline heart rate > 100 bpm or < 50 bpm
- Medical history of diseases with central nervous system (CNS)-involvement, including but not limited to stroke, traumatic brain injury, and loss of consciousness > 1 minute
- History of allergic reaction or medical contraindication to megestrol or phenytoin
- Clinically significant abnormalities on baseline labs (e.g. hypokalemia, hypernatremia, anemia)
- Lifetime history of an immunosuppressive disorder or immunosuppressive therapy with within the past 6 months
- History of blood clots such as myocardial infarction (MI), stroke, deep vein thromboses (DVTs), pulmonary embolism (PE) or blood clotting disorder
- Currently actively suicidal or considered a high suicide risk (e.g. more than one lifetime suicide attempt or any attempt in the past 12 months)
- Any reason not listed which, as determined by the principle investigator (PI), would affect participant safety in the study
Trial locations and contacts
1 site in 1 country.
About this study
This study is designed to test if megestrol acetate induces changes in declarative memory in healthy controls and if pre-administration of phenytoin can ameliorate any induced cognitive impairments.
Read the detailed description
Healthy adults (n=20) will be recruited and informed consent will be obtained. Participants will agree to a number of visits, a Baseline Visit, 6 Study Visits, and a follow-up Safety Visit. Each course of study drug will be followed by a washout, but allowed preexisting medications will not be stopped for study participation. A small subset (n=4) of participants will also undergo MRI scanning as a component of their visits following drug administration.
Baseline Visit: Cognition will be assessed by a variety of measures, which will determine baseline declarative memory and working memory. Mood will be assessed by a psychiatric interview, self-assessments, and a review of any standing physical symptoms will be completed for comparison to any side effects which develop after medication administration. Vital signs will be recorded and women will be screened for pregnancy. Blood will be collected for complete blood count (CBC) and comprehensive metabolic panel (CMP).
Visit 1: Participants will be randomized to one of three treatment possibilities: 1) phenytoin with megestrol, 2) placebo with megestrol, 3) placebo with placebo. Participants will receive phenytoin (200 mg BID) or placebo and will be instructed to take this medication for one full day (two doses) before starting their megestrol. They will take this medication for a total of 3.5 days.
Visit 2: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed. Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their next visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Visit 3: Participants will return and be randomized to one of remaining two treatment possibilities as detailed above. Participants will again be instructed to start the first medication and take for one full day before taking the second medication, and will be instructed to take their second medication at starting the following day after starting the first medication at 0900 hours and continue taking the drugs for 3 consecutive days.
Visit 4: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed; completing all previously administered assessments excepting the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID). Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their next visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Visit 5: Participants will return and receive the remaining treatment possibility, detailed above. Participants will again be instructed to start the first medication and take for one full day before taking the second medication and will be instructed to take their second medication at starting the following day after starting the first medication at 0900 hours and continue taking the drugs for 3 consecutive days.
Visit 6: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed. Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their final visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Safety Visit: Participants will return for a final "safety" visit which will evaluate any remaining side effects, take vital signs, and include a final urinary pregnancy test (for women).
- Conditions
- Cognitive Impairment
- Being tested
- Phenytoin 200 mg capsule, Megestrol 800 mg liquid, Phenytoin-matched Placebo capsule, Megestrol-matched liquid Placebo
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phenytoin 200 mg capsuleDrug
Phenytoin oral capsule was initiated on Day 1 and administered at 200 mg twice/day for four consecutive days (Days 1 - 4).
Megestrol 800 mg liquidDrug
Liquid megestrol 800 mg/was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).
Phenytoin-matched Placebo capsuleDrug
Phenytoin-matched oral Placebo capsule was initiated on Day 1 and administered for four consecutive days (Days 1 - 4).
Megestrol-matched liquid PlaceboDrug
Megestrol-matched liquid placebo was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).
| Study group | Role | What they receive |
|---|---|---|
| Phenytoin, Then Megestrol | Experimental | Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days. Receives: Drug: Phenytoin 200 mg capsule; Drug: Megestrol 800 mg liquid |
| Placebo, Then Megestrol | Experimental | Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days. Receives: Drug: Megestrol 800 mg liquid; Drug: Phenytoin-matched Placebo capsule |
| Placebo, Then Placebo | Experimental | Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days. Receives: Drug: Phenytoin-matched Placebo capsule; Drug: Megestrol-matched liquid Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rey Auditory Verbal Learning Test (RAVLT)
Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.
Measured: 4 days after intervention administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2015 (estimated)
- Study startJul 2015
- Primary completionNov 2016
- Study completionDec 2016
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.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant receives three treatments: phenytoin + megestrol, placebo + megestrol, or placebo + placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Rogosin Institute
- Responsible party
- Sponsor
- Investigators
- E. Sherwood Brown, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595723
- Sponsor's protocol ID
- 032015-004
- Status last verified
- Sep 2019
- First submitted
- 2 Jul 2015
- Last updated
- 9 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenytoin for Memory Impairment Secondary to Megestrol
- ClinicalTrials.gov ID
- NCT02595723
- Acronym / sponsor ID
- 032015-004
- Conditions
- Cognitive Impairment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- The Rogosin Institute
- Study start
- Jul 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 3 Nov 2015 (estimated)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to test if megestrol acetate induces changes in declarative memory in healthy controls and if pre-administration of phenytoin can ameliorate any induced cognitive impairments.
Detailed description
Healthy adults (n=20) will be recruited and informed consent will be obtained. Participants will agree to a number of visits, a Baseline Visit, 6 Study Visits, and a follow-up Safety Visit. Each course of study drug will be followed by a washout, but allowed preexisting medications will not be stopped for study participation. A small subset (n=4) of participants will also undergo MRI scanning as a component of their visits following drug administration.
Baseline Visit: Cognition will be assessed by a variety of measures, which will determine baseline declarative memory and working memory. Mood will be assessed by a psychiatric interview, self-assessments, and a review of any standing physical symptoms will be completed for comparison to any side effects which develop after medication administration. Vital signs will be recorded and women will be screened for pregnancy. Blood will be collected for complete blood count (CBC) and comprehensive metabolic panel (CMP).
Visit 1: Participants will be randomized to one of three treatment possibilities: 1) phenytoin with megestrol, 2) placebo with megestrol, 3) placebo with placebo. Participants will receive phenytoin (200 mg BID) or placebo and will be instructed to take this medication for one full day (two doses) before starting their megestrol. They will take this medication for a total of 3.5 days.
Visit 2: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed. Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their next visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Visit 3: Participants will return and be randomized to one of remaining two treatment possibilities as detailed above. Participants will again be instructed to start the first medication and take for one full day before taking the second medication, and will be instructed to take their second medication at starting the following day after starting the first medication at 0900 hours and continue taking the drugs for 3 consecutive days.
Visit 4: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed; completing all previously administered assessments excepting the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID). Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their next visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Visit 5: Participants will return and receive the remaining treatment possibility, detailed above. Participants will again be instructed to start the first medication and take for one full day before taking the second medication and will be instructed to take their second medication at starting the following day after starting the first medication at 0900 hours and continue taking the drugs for 3 consecutive days.
Visit 6: After the participants have completed their medication course on the morning of this visit day, they will return to have cognition and mood reassessed. Vital signs will be taken and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a "washout" period of this medicine combination (approximately 3 weeks) before returning for their final visit. For those participants offered the MRI scans, their visit will extend to approximately 3 hours.
Safety Visit: Participants will return for a final "safety" visit which will evaluate any remaining side effects, take vital signs, and include a final urinary pregnancy test (for women).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Each participant receives three treatments: phenytoin + megestrol, placebo + megestrol, or placebo + placebo
| Arm | Type | Receives |
|---|---|---|
| Phenytoin, Then Megestrol | Experimental | Drug: Phenytoin 200 mg capsule, Drug: Megestrol 800 mg liquidParticipants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days. |
| Placebo, Then Megestrol | Experimental | Drug: Megestrol 800 mg liquid, Drug: Phenytoin-matched Placebo capsuleParticipants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days. |
| Placebo, Then Placebo | Experimental | Drug: Phenytoin-matched Placebo capsule, Drug: Megestrol-matched liquid PlaceboParticipants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy men and women age 18-50 years
- Education of ≥ 12 years and baseline Rey Auditory Verbal Learning Test (RAVLT) total words recalled score ≥ 40 (normal baseline memory)
- Body mass index (BMI) between 18.5-35
- The ability to read and speak English as not all neurocognitive assessments have been translated and validated in other languages.
Key exclusion criteria (17 listed)
- History (lifetime) of Bipolar Disorder, Major Depressive Disorder, psychotic depressive, schizophrenic, schizoaffective, or other Axis I psychotic disorders
- Has an unstable general medical condition (GMC) or significant medical condition, including but not limited to myocardial infarction, cancer, diabetes (hypertension is allowed if condition is being treated and is stable)
- Vulnerable populations including pregnant or nursing women, the incarcerated, or those with severe cognitive disorders
- Education history that includes Special Education or history of mental disability
- History of psychotropic medication therapy in the past 30 days
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 |
|---|---|---|
| Phenytoin 200 mg capsulePhenytoin oral capsule was initiated on Day 1 and administered at 200 mg twice/day for four consecutive days (Days 1 - 4). | Drug | Phenytoin, Then Megestrol |
| Megestrol 800 mg liquidLiquid megestrol 800 mg/was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4). | Drug | Phenytoin, Then Megestrol, Placebo, Then Megestrol |
| Phenytoin-matched Placebo capsulePhenytoin-matched oral Placebo capsule was initiated on Day 1 and administered for four consecutive days (Days 1 - 4). | Drug | Placebo, Then Megestrol, Placebo, Then Placebo |
| Megestrol-matched liquid PlaceboMegestrol-matched liquid placebo was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4). | Drug | Placebo, Then Placebo |
Primary outcome
Rey Auditory Verbal Learning Test (RAVLT)
Time frame: 4 days after intervention administration
Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
E. Sherwood Brown, MD, PhD principal investigator
University of Texas Southwestern Medical Center
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 Phenytoin 200 mg capsule and Megestrol 800 mg liquid in people with Cognitive Impairment, run by University of Texas Southwestern Medical Center 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 4 inclusion and 17 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 9 Sep 2019. 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 9 Sep 2019). 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?
Rey Auditory Verbal Learning Test (RAVLT) (time frame: 4 days after intervention administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2019.