- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02258828
An Open-Label Trial of Memantine for Cognitive Impairment in Patients With Post-Traumatic Stress Disorder
Study Overview
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Nebraska
-
Omaha, Nebraska, United States, 68105
- Omaha Veterans Affairs Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Memantine
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
|
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
Other Names:
|
Placebo Comparator: Placebo
Patient received matched placebo
|
Matched placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
RBANS
Time Frame: 16 WEEKS
|
16 WEEKS
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Neurocognitive Disorders
- Trauma and Stressor Related Disorders
- Cognition Disorders
- Stress Disorders, Traumatic
- Stress Disorders, Post-Traumatic
- Cognitive Dysfunction
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Memantine
Other Study ID Numbers
- 00255
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on PTSD
-
University of PittsburghCompletedPTSD | Non PTSDUnited States
-
Imperial College Healthcare NHS TrustImperial College LondonRecruiting
-
VA Office of Research and DevelopmentUniversity of California, San DiegoRecruiting
-
University of Wisconsin, MadisonNational Institute of Mental Health (NIMH)Active, not recruiting
-
Oregon Health and Science UniversityEnrolling by invitation
-
VA Office of Research and DevelopmentCompleted
-
VA Office of Research and DevelopmentPortland VA Medical CenterActive, not recruiting
-
VA Office of Research and DevelopmentSan Diego Veterans Healthcare SystemCompleted
-
Creighton UniversityCompleted
-
VA Eastern KansasTerminated
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States