<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02258828</url>
  </required_header>
  <id_info>
    <org_study_id>00255</org_study_id>
    <nct_id>NCT02258828</nct_id>
  </id_info>
  <brief_title>An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder</brief_title>
  <official_title>An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sriram Ramaswamy</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Forest Laboratories</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Nebraska Western Iowa Health Care System</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Twenty six veterans with PTSD and cognitive impairment received 16 weeks of memantine in an&#xD;
      open label fashion. Cognition was assessed using the Spatial Span, Logical Memory I, and&#xD;
      Letter-Number Sequencing subtests of the Wechsler Memory Scale III (Third edition) and the&#xD;
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RBANS measures&#xD;
      attention, language, visuospatial skills, and immediate and delayed memories. The Clinician&#xD;
      Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale&#xD;
      (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan&#xD;
      Disability Scale (SDS) were used to assess improvement in PTSD symptoms, as secondary outcome&#xD;
      measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants were recruited from the Omaha Veterans Affairs Medical Center following local&#xD;
      IRB approval. We obtained written consent from all the subjects who were recruited in the&#xD;
      study. Veterans between the ages of 19 and 65 years with chronic PTSD (diagnosis for &gt;6&#xD;
      months) attributable to military combat exposure were included in the study. Patients were&#xD;
      required to be clinically stable on their psychotropic medication regimen for at least three&#xD;
      months prior to study entry. In addition to meeting DSM-IV criteria for PTSD and endorsing&#xD;
      subjective complaints of memory difficulties, patients had to score least one standard&#xD;
      deviation below the mean performance of a standardized, age- and sex-matched population on&#xD;
      the Spatial Span, Logical Memory I, and Letter-Number Sequencing subtests of the Wechsler&#xD;
      Memory Scale III (Third edition) for study entry. Patients with a history of dementia,&#xD;
      schizophrenia, bipolar disorder, traumatic brain injury, and seizure were excluded. Patients&#xD;
      with any history of alcohol or illicit drug abuse or dependence within the past one month&#xD;
      were excluded. Patients requiring concomitant treatment with drugs with potential effects on&#xD;
      the glutamergic system, such as amantadine,dextromethorphan, or carbonic anhydrase&#xD;
      inhibitors, were excluded.&#xD;
&#xD;
      Subjects initially received memantine 5 mg once daily, which was increased weekly by 5 mg/day&#xD;
      in divided doses to a dose of 20 mg/day. Memory was assessed using the Repeatable Battery for&#xD;
      the Assessment of Neuropsychological Status (RBANS) [Randolph, 1998] using both forms A and B&#xD;
      at baseline, end of week 8, and end of week 16. The RBANS is composed of 10 subtests that&#xD;
      yield a total score and five index scores: immediate memory, visuospatial/constructional,&#xD;
      language, attention, and delayed memory. Each index score has a normal mean of 100 and&#xD;
      standard deviation of 15 based on the performance of a standardization sample matched to the&#xD;
      U.S. Census on sex, ethnicity, and level of education. Alternative forms of the RBANS (Forms&#xD;
      A and B) were used to avoid bias due to practice effects. We administered Clinician&#xD;
      Administered PTSD Scale (CAPS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale&#xD;
      (HAM-A), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and Sheehan&#xD;
      Disability Scale (SDS) to assess the secondary measures. Changes in the scores over time with&#xD;
      repeated measures were estimated with mixed-effects models. The primary outcome measures of&#xD;
      interest were index and percentile scores in RBANS total and subscale scores. The repeated&#xD;
      measures model included visit (as a categorical variable) as a fixed effect. An unstructured&#xD;
      covariance matrix was used to fit the within patient repeated measures effect. Tukey's method&#xD;
      was used to compare pair-wise means.&#xD;
&#xD;
      Secondary outcome measures, CAPS, HAM-A, HAM-D, Q-LES-Q, and SDS, were analyzed similarly to&#xD;
      the RBANS with repeated measures models. P-values less than 0.05 are considered to be&#xD;
      statistically significant. SAS software version 9.1 (SAS Institute, Cary, NC) was used for&#xD;
      the analysis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2005</start_date>
  <completion_date type="Actual">March 2007</completion_date>
  <primary_completion_date type="Actual">March 2007</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>RBANS</measure>
    <time_frame>16 WEEKS</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>PTSD</condition>
  <arm_group>
    <arm_group_label>Memantine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient received matched placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Memantine</intervention_name>
    <description>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</description>
    <arm_group_label>Memantine</arm_group_label>
    <other_name>Namenda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients, men and women between 18 and 65 years of age, inclusive.&#xD;
&#xD;
          2. Patients with diagnosis of Posttraumatic Stress Disorder (309.81) for at least 6&#xD;
             months, as determined by the Structured Clinical Interview for DSM-IV Axis 1 Disorders&#xD;
             (SCID).&#xD;
&#xD;
          3. Patients with a score of at least 1 standard deviation below the mean on the Spatial&#xD;
             Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory&#xD;
             Scale III (Third edition).&#xD;
&#xD;
          4. Patients, who are able to comprehend and satisfactorily comply with protocol&#xD;
             requirements and have an ability to read and write English,&#xD;
&#xD;
          5. Patients, who signed the written informed consent given prior to entering any study&#xD;
             procedure.&#xD;
&#xD;
          6. Patients must be clinically stable on their medications for past three months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a concurrent DSM-IV Axis I or Axis II diagnosis in any of the following&#xD;
             categories:&#xD;
&#xD;
               -  1.1. Delirium, Dementia, Amnestic and other Cognitive disorders&#xD;
&#xD;
               -  1.2. Mental Retardation&#xD;
&#xD;
               -  1.3. Lifetime Schizophrenia and other Psychotic Disorders&#xD;
&#xD;
               -  1.4. Lifetime Bipolar I Disorder&#xD;
&#xD;
               -  1.5. Alcohol or Substance Dependence or Abuse (excluding nicotine) in one month&#xD;
                  prior to the Screening Visit&#xD;
&#xD;
               -  1.6. Any other concurrent Axis I Disorder (including Major Depressive Disorder)&#xD;
                  must be secondary to the primary diagnosis of PTSD.&#xD;
&#xD;
          2. Patients with a score of less than 1 standard deviation below the mean on the Spatial&#xD;
             Span, Logical Memory I and Letter-Number Sequencing subtest's of the Wechsler Memory&#xD;
             Scale III at the screening visit.&#xD;
&#xD;
          3. Patients with a history of treatment with cholinesterase inhibitor drugs like&#xD;
             donezepil, galantamine or rivigstamine.&#xD;
&#xD;
          4. Patients with a history of intolerance or hypersensitivity to memantine.&#xD;
&#xD;
          5. Patients with a history of seizures and traumatic head injury.&#xD;
&#xD;
          6. Patients requiring concomitant treatment amantadine or dextromethorphan or carbonic&#xD;
             anhydrase inhibitors.&#xD;
&#xD;
          7. Patients who based on history or mental status examination have a significant risk of&#xD;
             committing suicide.&#xD;
&#xD;
          8. Patients who are homicidal or violent and who are in the Investigator's opinion in&#xD;
             significant imminent risk of hurting others.&#xD;
&#xD;
          9. Patients with a positive urine drug screen, for drugs of abuse.&#xD;
&#xD;
         10. Patients who have participated in any clinical trial within one month prior to the&#xD;
             Screening Visit, or in a clinical trial involving a psychotropic medication within the&#xD;
             3 months prior to the Screening Visit.&#xD;
&#xD;
         11. Patients who have a medical condition that, in the Investigator's opinion, would&#xD;
             expose them to an increased risk of a significant adverse event or interfere with&#xD;
             assessments of safety and efficacy during the course of the trial.&#xD;
&#xD;
         12. Patients with any current malignancy, or any clinically significant hematological,&#xD;
             endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease&#xD;
             (including any form of epilepsy). If there is a history of such disease but the&#xD;
             condition has been stable for at least the past year and is judged by the investigator&#xD;
             not to interfere with the patient's participation in the study, the patient may be&#xD;
             included.&#xD;
&#xD;
         13. Patients whose laboratory values at the Screening visit will be 2 times greater than&#xD;
             ULN.&#xD;
&#xD;
         14. Patients who require concomitant therapy with any prohibited prescription or&#xD;
             over-the-counter medication.&#xD;
&#xD;
         15. Patients who are unable to speak, read, and understand English or are judged by the&#xD;
             investigator to be unable or unlikely to follow the study protocol and complete all&#xD;
             scheduled visits.&#xD;
&#xD;
         16. Women patients who are pregnant, planning to become pregnant, or if of childbearing&#xD;
             potential, not using an acceptable method of birth control.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sriram Ramaswamy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Veterans Affairs/NWIHCS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Omaha Veterans Affairs Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>May 20, 2020</last_update_submitted>
  <last_update_submitted_qc>May 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>VA Nebraska Western Iowa Health Care System</investigator_affiliation>
    <investigator_full_name>Sriram Ramaswamy</investigator_full_name>
    <investigator_title>STAFF PSYCHIATRIST</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Memantine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02258828
org study id: 00255
nct id: NCT02258828
lead sponsor: 
collaborator: 
has dmc: No
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.
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: RBANS
time frame: 16 WEEKS
arm group label: Memantine
arm group type: Experimental
description: 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
arm group label: Placebo
arm group type: Placebo Comparator
description: Patient received matched placebo
intervention type: Drug
intervention name: Memantine
description: 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
arm group label: Memantine
other name: Namenda
intervention type: Drug
intervention name: Placebo
description: Matched placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: No
last name: Sriram Ramaswamy, MD
role: Principal Investigator
affiliation: Department of Veterans Affairs/NWIHCS
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: VA Nebraska Western Iowa Health Care System
investigator full name: Sriram Ramaswamy
investigator title: STAFF PSYCHIATRIST
mesh term: Cognitive Dysfunction
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
mesh term: Memantine
sharing ipd: Yes