Back to resultsMemantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus (ClearMEMory)
Primary Purpose
Lupus Erythematosus, Systemic
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring cognitive dysfunction, memantine, lupus
Eligibility Criteria
Inclusion Criteria:
- Meet American College of Rheumatology (ACR) criteria for SLE
- Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to the psychiatric manifestations questions
- Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)
Exclusion Criteria:
- Male and female subjects <18 or >60 years
- Change in medication that may affect mood or cognition including prednisone, antidepressant medications, or stimulants within the last 4 weeks
- Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use
- Metabolic derangement defined as liver function tests >3x upper limit of normal or severe renal disease defined as calculated creatinine clearance <30 mL
- Severe psychiatric disease including schizophrenia, psychosis, suicidal depression
- Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history)* or prevent the participant from completing the protocol (poor compliance or unpredictable schedule)
- Inability or refusal to give informed consent for any reason including a diagnosis of dementia or significant cognitive impairment**
- Patients who are pregnant
- Patients who are enrolled in other investigational drug studies
Sites / Locations
- Vanderbilt University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Memantine
Placebo
Arm Description
At randomization, subjects will receive 5 mg twice per day for one week. They will escalate their dose to 10 mg twice per day for one week, then 10 mg in the morning and 20 mg at night for one week, and finally 20 mg twice per day for three weeks. Maximum tolerated will be determined at this time and this dose will be continued for an additional six weeks.
At randomization, subjects will receive one matching placebo capsule twice per day for one week. They will also take one matching placebo capsule twice per day for the next week (week 2), then one matching placebo capsule in the morning and two capsules at night for one week (week three), and finally two capsules twice per day for three weeks (weeks 4-6). Maximum tolerated number of capsules will be determined at this time and this dose will be continued for an additional six weeks.
Outcomes
Primary Outcome Measures
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
RBANS is a widely used psychiatric tool that objectively measures cognitive impairment. It is comprised of 12 subtests and takes approximately 30 minutes. For scoring, the RBANS index scores are converted to classifications including Very Superior (130 and above), Superior (120-129), High Average (110-119), Average (90-109), Low Average (80-89), Borderline (70-79), and Extremely Low (69 and below). A score of Extremely Low equates to severe cognitive impairment. The primary outcome measure will be analyzed using ANCOVA controlling for memantine/placebo, baseline RBANS, sex, age, and NMDAR status.
Secondary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
We will determine the safety of memantine as measured by treatment-emergent adverse events.
Polysymptomatic Distress Scale
The Polysymptomatic Distress (PSD) scale measures the effect of PSD over a range of pain-related clinical symptoms. The scale was derived from variables used in the 2010 American College of Rheumatology fibromyalgia criteria, modified for use in clinical research, and broadened to be applicable for patients not meeting fibromyalgia diagnostic criteria. The PSD score is calculated by summing two components, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS). The WPI is a count of painful nonarticular body regions, and the SSS is a symptom severity measure that includes fatigue, sleep, and cognitive problems.
Beck Depression Inventory
The Beck Depression Inventory (BDI) is a 21-item, self-report inventory that measures depression symptoms and attitudes. It takes approximately 10 minutes to complete and requires a fifth to sixth grade reading level to adequately comprehend the questions.
Hospital Anxiety and Depression Scale
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale and was developed to detect states of depression, anxiety, and emotional distress among patients who were being treated for a variety of clinical problems. The scale has a total of 14 items, with responses being scored on a scale of 0-3 (3 indicates higher symptom frequencies). Scores for each subscale (anxiety and depression) range from 0 to 21, categorized as follows: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K
SLEDAI-2K is an updated version of the SLEDAI which was originally developed in 1985 as a clinical index to assess lupus disease activity in the preceding 10 days. It is a cumulative and weighted index of 24 different clinical and laboratory variables/disease descriptors, comprising 9 organ systems. The Investigator will assess disease descriptors on the SLEDAI-2K collection sheet (e.g., arthritis, myositis, alopecia, rash, mucosal ulcers, etc.).
Patient Global Impression of Change
Participants will answer the standard question, "Considering all the ways your health affects you, how are you doing since the beginning of your treatment?" Answers include very much worse, much worse, worse, unchanged, improved, much improved, and very much improved.
RBANS Subscales
Our primary outcome is the RBANS Total Index Score, which is the sum of several subscales/tests. For a secondary outcome, we will look at each subscale/test individually to see if there is a trend for any one test in particular. The subscales are all scored the same (40 - 160) and include immediate memory, delayed memory, visuospatial/constructional, language, and attention.
Full Information
NCT ID
NCT03527472
First Posted
May 3, 2018
Last Updated
May 18, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
Evergreen Therapeutics, Inc., The University of Texas Health Science Center, Houston, The Cleveland Clinic
1. Study Identification
Unique Protocol Identification Number
NCT03527472
Brief Title
Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
Acronym
ClearMEMory
Official Title
A Randomized Placebo-controlled, Double Blind Phase 2 Clinical Trial of Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 23, 2018 (Actual)
Primary Completion Date
June 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Evergreen Therapeutics, Inc., The University of Texas Health Science Center, Houston, The Cleveland Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A phenome-wide association study (PheWAS) identified an association between a variant in the human gene for the N2A subunit of the N-methyl-D-aspartate (NMDA) receptor, GRIN2A, and Systemic Lupus Erythematosus (SLE). A single nucleotide polymorphism (SNP) in this gene encodes for increased NMDA receptor activity. Based on the potential function of the associated SNP and published literature, alterations in SNP function signaling may underlie a cluster of symptoms. The objective of this study is to evaluate the safety, tolerability and efficacy of memantine, an NMDA receptor antagonist, in a precise patient subset with SLE. Participants will complete a full 14-week clinical trial, receiving either memantine or a placebo. Participants' blood will be drawn to test for various antibodies as well as organ function. Patients' urine will also be collected to assess organ function and pregnancy for females at a number of specific time points. The overall goal is to develop a safe and inexpensive therapeutic approach to reduce debilitating cognitive symptoms in a precisely selected SLE sub-population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
Keywords
cognitive dysfunction, memantine, lupus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind, randomized, placebo-controlled
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Memantine
Arm Type
Experimental
Arm Description
At randomization, subjects will receive 5 mg twice per day for one week. They will escalate their dose to 10 mg twice per day for one week, then 10 mg in the morning and 20 mg at night for one week, and finally 20 mg twice per day for three weeks. Maximum tolerated will be determined at this time and this dose will be continued for an additional six weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
At randomization, subjects will receive one matching placebo capsule twice per day for one week. They will also take one matching placebo capsule twice per day for the next week (week 2), then one matching placebo capsule in the morning and two capsules at night for one week (week three), and finally two capsules twice per day for three weeks (weeks 4-6). Maximum tolerated number of capsules will be determined at this time and this dose will be continued for an additional six weeks.
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Namenda
Intervention Description
Memantine is an FDA-approved drug for the treatment of Alzheimer's disease.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (memantine).
Primary Outcome Measure Information:
Title
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
Description
RBANS is a widely used psychiatric tool that objectively measures cognitive impairment. It is comprised of 12 subtests and takes approximately 30 minutes. For scoring, the RBANS index scores are converted to classifications including Very Superior (130 and above), Superior (120-129), High Average (110-119), Average (90-109), Low Average (80-89), Borderline (70-79), and Extremely Low (69 and below). A score of Extremely Low equates to severe cognitive impairment. The primary outcome measure will be analyzed using ANCOVA controlling for memantine/placebo, baseline RBANS, sex, age, and NMDAR status.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
We will determine the safety of memantine as measured by treatment-emergent adverse events.
Time Frame
12 weeks
Title
Polysymptomatic Distress Scale
Description
The Polysymptomatic Distress (PSD) scale measures the effect of PSD over a range of pain-related clinical symptoms. The scale was derived from variables used in the 2010 American College of Rheumatology fibromyalgia criteria, modified for use in clinical research, and broadened to be applicable for patients not meeting fibromyalgia diagnostic criteria. The PSD score is calculated by summing two components, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS). The WPI is a count of painful nonarticular body regions, and the SSS is a symptom severity measure that includes fatigue, sleep, and cognitive problems.
Time Frame
12 weeks
Title
Beck Depression Inventory
Description
The Beck Depression Inventory (BDI) is a 21-item, self-report inventory that measures depression symptoms and attitudes. It takes approximately 10 minutes to complete and requires a fifth to sixth grade reading level to adequately comprehend the questions.
Time Frame
12 weeks
Title
Hospital Anxiety and Depression Scale
Description
The Hospital Anxiety and Depression Scale (HADS) is a self-assessment scale and was developed to detect states of depression, anxiety, and emotional distress among patients who were being treated for a variety of clinical problems. The scale has a total of 14 items, with responses being scored on a scale of 0-3 (3 indicates higher symptom frequencies). Scores for each subscale (anxiety and depression) range from 0 to 21, categorized as follows: normal 0-7, mild 8-10, moderate 11-14, and severe 15-21.
Time Frame
12 weeks
Title
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K
Description
SLEDAI-2K is an updated version of the SLEDAI which was originally developed in 1985 as a clinical index to assess lupus disease activity in the preceding 10 days. It is a cumulative and weighted index of 24 different clinical and laboratory variables/disease descriptors, comprising 9 organ systems. The Investigator will assess disease descriptors on the SLEDAI-2K collection sheet (e.g., arthritis, myositis, alopecia, rash, mucosal ulcers, etc.).
Time Frame
12 weeks
Title
Patient Global Impression of Change
Description
Participants will answer the standard question, "Considering all the ways your health affects you, how are you doing since the beginning of your treatment?" Answers include very much worse, much worse, worse, unchanged, improved, much improved, and very much improved.
Time Frame
Endpoint (Visit 4)
Title
RBANS Subscales
Description
Our primary outcome is the RBANS Total Index Score, which is the sum of several subscales/tests. For a secondary outcome, we will look at each subscale/test individually to see if there is a trend for any one test in particular. The subscales are all scored the same (40 - 160) and include immediate memory, delayed memory, visuospatial/constructional, language, and attention.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Meet American College of Rheumatology (ACR) criteria for SLE
Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to the psychiatric manifestations questions
Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)
Exclusion Criteria:
Male and female subjects <18 or >60 years
Change in medication that may affect mood or cognition including prednisone, antidepressant medications, or stimulants within the last 4 weeks
Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use
Metabolic derangement defined as liver function tests >3x upper limit of normal or severe renal disease defined as calculated creatinine clearance <30 mL
Severe psychiatric disease including schizophrenia, psychosis, suicidal depression
Other factors which in the opinion of the investigator could potentially impact the study outcomes (e.g., underlying disease, medications, history)* or prevent the participant from completing the protocol (poor compliance or unpredictable schedule)
Inability or refusal to give informed consent for any reason including a diagnosis of dementia or significant cognitive impairment**
Patients who are pregnant
Patients who are enrolled in other investigational drug studies
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jonathan M Williams, PhD
Phone
6158759200
Email
jon.williams@vumc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Jana K Shirey-Rice, PhD
Phone
6153227022
Email
jana.shirey@vumc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leslie J Crofford, MD
Organizational Affiliation
Professor of Medicine - Rheumatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jon Williams, PhD
Phone
615-875-9200
Email
jon.williams@vumc.org
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
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