PTSDPhase 4NCT02258828
An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder
A Phase 4 study testing Memantine in people with PTSD, run by Sriram Ramaswamy at 1 site in United States.
Trial summary
Twenty six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) and the Repeatable Battery for the Assessment of… Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- PTSD
- What is being tested?
- Memantine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Mar 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients, men and women between 18 and 65 years of age, inclusive.
- Patients with diagnosis of Posttraumatic Stress Disorder (309.81) for at least 6 months, as determined by the Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID).
- Patients with a score of at least 1 standard deviation below the mean on the Spatial Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory Scale III (Third edition).
- Patients, who are able to comprehend and satisfactorily comply with protocol requirements and have an ability to read and write English,
- Patients, who signed the written informed consent given prior to entering any study procedure.
- Patients must be clinically stable on their medications for past three months
Who cannot join
- Patients with a concurrent DSM-IV Axis I or Axis II diagnosis in any of the following categories:
- 1.1. Delirium, Dementia, Amnestic and other Cognitive disorders
- 1.2. Mental Retardation
- 1.3. Lifetime Schizophrenia and other Psychotic Disorders
- 1.4. Lifetime Bipolar I Disorder
- 1.5. Alcohol or Substance Dependence or Abuse (excluding nicotine) in one month prior to the Screening Visit
Show all 22Show fewer
- 1.6. Any other concurrent Axis I Disorder (including Major Depressive Disorder) must be secondary to the primary diagnosis of PTSD.
- Patients with a score of less than 1 standard deviation below the mean on the Spatial Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory Scale III at the screening visit.
- Patients with a history of treatment with cholinesterase inhibitor drugs like donezepil, galantamine or rivigstamine.
- Patients with a history of intolerance or hypersensitivity to memantine.
- Patients with a history of seizures and traumatic head injury.
- Patients requiring concomitant treatment amantadine or dextromethorphan or carbonic anhydrase inhibitors.
- Patients who based on history or mental status examination have a significant risk of committing suicide.
- Patients who are homicidal or violent and who are in the Investigator's opinion in significant imminent risk of hurting others.
- Patients with a positive urine drug screen, for drugs of abuse.
- Patients who have participated in any clinical trial within one month prior to the Screening Visit, or in a clinical trial involving a psychotropic medication within the 3 months prior to the Screening Visit.
- Patients who have a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial.
- Patients with any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease (including any form of epilepsy). If there is a history of such disease but the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
- Patients whose laboratory values at the Screening visit will be 2 times greater than ULN.
- Patients who require concomitant therapy with any prohibited prescription or over-the-counter medication.
- Patients who are unable to speak, read, and understand English or are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits.
- Women patients who are pregnant, planning to become pregnant, or if of childbearing potential, not using an acceptable method of birth control.
Trial locations and contacts
1 site in 1 country.
United States1 site
Omaha Veterans Affairs Medical Center
Omaha, Nebraska, 68105
About this study
Twenty six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) were used to assess improvement in PTSD symptoms, as secondary outcome measures.
Read the detailed description
Participants were recruited from the Omaha Veterans Affairs Medical Center following local IRB approval. We obtained written consent from all the subjects who were recruited in the study. Veterans between the ages of 19 and 65 years with chronic PTSD (diagnosis for >6 months) attributable to military combat exposure were included in the study. Patients were required to be clinically stable on their psychotropic medication regimen for at least three months prior to study entry. In addition to meeting DSM-IV criteria for PTSD and endorsing subjective complaints of memory difficulties, patients had to score least one standard deviation below the mean performance of a standardized, age- and sex-matched population on the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) for study entry. Patients with a history of dementia, schizophrenia, bipolar disorder, traumatic brain injury, and seizure were excluded. Patients with any history of alcohol or illicit drug abuse or dependence within the past one month were excluded. Patients requiring concomitant treatment with drugs with potential effects on the glutamergic system, such as amantadine,dextromethorphan, or carbonic anhydrase inhibitors, were excluded.
Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day. Memory was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Randolph, 1998] using both forms A and B at baseline, end of week 8, and end of week 16. The RBANS is composed of 10 subtests that yield a total score and five index scores: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Each index score has a normal mean of 100 and standard deviation of 15 based on the performance of a standardization sample matched to the U.S. Census on sex, ethnicity, and level of education. Alternative forms of the RBANS (Forms A and B) were used to avoid bias due to practice effects. We administered Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) to assess the secondary measures. Changes in the scores over time with repeated measures were estimated with mixed-effects models. The primary outcome measures of interest were index and percentile scores in RBANS total and subscale scores. The repeated measures model included visit (as a categorical variable) as a fixed effect. An unstructured covariance matrix was used to fit the within patient repeated measures effect. Tukey's method was used to compare pair-wise means.
Secondary outcome measures, CAPS, HAM-A, HAM-D, Q-LES-Q, and SDS, were analyzed similarly to the RBANS with repeated measures models. P-values less than 0.05 are considered to be statistically significant. SAS software version 9.1 (SAS Institute, Cary, NC) was used for the analysis
- Conditions
- PTSD
- Being tested
- Memantine, Placebo
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
Also called Namenda
Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Memantine | Experimental | Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day Receives: Drug: Memantine |
| Placebo | Placebo comparator | Patient received matched placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
RBANS
Measured: 16 WEEKS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study startJul 2005
- Primary completionMar 2007
- Study completionMar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSDStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sriram Ramaswamy
- Sponsor type
- US federal agency
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor-investigator, Sriram Ramaswamy, VA Nebraska Western Iowa Health Care System
- Investigators
- Sriram Ramaswamy, MD, Principal investigator, Department of Veterans Affairs/NWIHCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258828
- Sponsor's protocol ID
- 00255
- Status last verified
- May 2020
- First submitted
- 2 Oct 2014
- Last updated
- 22 May 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT02258828
- Acronym / sponsor ID
- 00255
- Conditions
- PTSD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Sriram RamaswamyUS federal agency
- Collaborators
- Forest Laboratories
- Study start
- Jul 2005
- Primary completion
- Mar 2007 (actual)
- Study completion
- Mar 2007 (actual)
- First posted
- 8 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Twenty six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an open label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures attention, language, visuospatial skills, and immediate and delayed memories. The Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) were used to assess improvement in PTSD symptoms, as secondary outcome measures.
Detailed description
Participants were recruited from the Omaha Veterans Affairs Medical Center following local IRB approval. We obtained written consent from all the subjects who were recruited in the study. Veterans between the ages of 19 and 65 years with chronic PTSD (diagnosis for >6 months) attributable to military combat exposure were included in the study. Patients were required to be clinically stable on their psychotropic medication regimen for at least three months prior to study entry. In addition to meeting DSM-IV criteria for PTSD and endorsing subjective complaints of memory difficulties, patients had to score least one standard deviation below the mean performance of a standardized, age- and sex-matched population on the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) for study entry. Patients with a history of dementia, schizophrenia, bipolar disorder, traumatic brain injury, and seizure were excluded. Patients with any history of alcohol or illicit drug abuse or dependence within the past one month were excluded. Patients requiring concomitant treatment with drugs with potential effects on the glutamergic system, such as amantadine,dextromethorphan, or carbonic anhydrase inhibitors, were excluded.
Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day. Memory was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [Randolph, 1998] using both forms A and B at baseline, end of week 8, and end of week 16. The RBANS is composed of 10 subtests that yield a total score and five index scores: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Each index score has a normal mean of 100 and standard deviation of 15 based on the performance of a standardization sample matched to the U.S. Census on sex, ethnicity, and level of education. Alternative forms of the RBANS (Forms A and B) were used to avoid bias due to practice effects. We administered Clinician Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan Disability Scale (SDS) to assess the secondary measures. Changes in the scores over time with repeated measures were estimated with mixed-effects models. The primary outcome measures of interest were index and percentile scores in RBANS total and subscale scores. The repeated measures model included visit (as a categorical variable) as a fixed effect. An unstructured covariance matrix was used to fit the within patient repeated measures effect. Tukey's method was used to compare pair-wise means.
Secondary outcome measures, CAPS, HAM-A, HAM-D, Q-LES-Q, and SDS, were analyzed similarly to the RBANS with repeated measures models. P-values less than 0.05 are considered to be statistically significant. SAS software version 9.1 (SAS Institute, Cary, NC) was used for the analysis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Memantine | Experimental | Drug: MemantineSubjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day |
| Placebo | Placebo comparator | Drug: PlaceboPatient received matched placebo |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients, men and women between 18 and 65 years of age, inclusive.
- Patients with diagnosis of Posttraumatic Stress Disorder (309.81) for at least 6 months, as determined by the Structured Clinical Interview for DSM-IV Axis 1 Disorders (SCID).
- Patients with a score of at least 1 standard deviation below the mean on the Spatial Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory Scale III (Third edition).
- Patients, who are able to comprehend and satisfactorily comply with protocol requirements and have an ability to read and write English,
- Patients, who signed the written informed consent given prior to entering any study procedure.
Key exclusion criteria (22 listed)
- Patients with a concurrent DSM-IV Axis I or Axis II diagnosis in any of the following categories:
- Patients with a score of less than 1 standard deviation below the mean on the Spatial Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory Scale III at the screening visit.
- Patients with a history of treatment with cholinesterase inhibitor drugs like donezepil, galantamine or rivigstamine.
- Patients with a history of intolerance or hypersensitivity to memantine.
- Patients with a history of seizures and traumatic head injury.
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 |
|---|---|---|
| MemantineAlso: NamendaSubjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day | Drug | Memantine |
| PlaceboMatched placebo | Drug | Placebo |
Primary outcome
RBANS
Time frame: 16 WEEKS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2020.
- Individual participant dataSharing planned: Yes
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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.
Sriram Ramaswamy, MD principal investigator
Department of Veterans Affairs/NWIHCS
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 Memantine in people with PTSD, run by Sriram Ramaswamy 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 6 inclusion and 22 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 22 May 2020. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
RBANS (time frame: 16 WEEKS). 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 22 May 2020.