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Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus (ClearMEMory)

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ClinicalTrials.gov Identifier: NCT03527472
Recruitment Status : Recruiting
First Posted : May 17, 2018
Last Update Posted : September 25, 2018
Sponsor:
Collaborator:
Kleberg Foundation
Information provided by (Responsible Party):
Leslie Crofford, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE May 3, 2018
First Posted Date  ICMJE May 17, 2018
Last Update Posted Date September 25, 2018
Actual Study Start Date  ICMJE August 23, 2018
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4) [ Time Frame: 12 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
Change in the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
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.
Change History Complete list of historical versions of study NCT03527472 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 12 weeks ]
    We will determine the safety of memantine as measured by treatment-emergent adverse events.
  • Polysymptomatic Distress Scale [ Time Frame: 12 weeks ]
    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 [ Time Frame: 12 weeks ]
    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 [ Time Frame: 12 weeks ]
    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 [ Time Frame: 12 weeks ]
    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 [ Time Frame: Endpoint (Visit 4) ]
    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 [ Time Frame: 12 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    We will determine the safety of memantine as measured by treatment-emergent adverse events.
  • Polysymptomatic Distress Scale [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    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 [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    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 [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    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 [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    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 [ Time Frame: Endpoint (Visit 4) ]
    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 [ Time Frame: Baseline (Visit 1) to Endpoint (Visit 4) - 12 weeks ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
Official Title  ICMJE A Randomized Placebo-controlled, Double Blind Phase 2 Clinical Trial of Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind, randomized, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lupus Erythematosus, Systemic
Intervention  ICMJE
  • Drug: Memantine
    Memantine is an FDA-approved drug for the treatment of Alzheimer's disease.
    Other Name: Namenda
  • Drug: Placebo
    The placebo will match the study drug in appearance, dose, and frequency. It will not contain any active drug (memantine).
Study Arms  ICMJE
  • Experimental: Memantine
    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.
    Intervention: Drug: Memantine
  • Placebo Comparator: Placebo
    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: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 15, 2018)
144
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Meet American College of Rheumatology (ACR) criteria for SLE
  2. Report NPSLE symptoms on the screening survey recommended by EULAR guideline but limited to the psychiatric manifestations questions
  3. Score ≤ 85 on the RBANS total index (≤ 1 SD below the normative mean of 100)

Exclusion Criteria:

  1. Male and female subjects <18 or >60 years
  2. Change in medication that may affect mood or cognition including prednisone, antidepressant medications, or stimulants within the last 4 weeks
  3. Regular (daily) use of opioids or other drugs of abuse including heavy alcohol or marijuana use
  4. Metabolic derangement defined as liver function tests >3x upper limit of normal or severe renal disease defined as calculated creatinine clearance <30 mL
  5. Severe psychiatric disease including schizophrenia, psychosis, suicidal depression
  6. 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)
  7. Inability or refusal to give informed consent for any reason including a diagnosis of dementia or significant cognitive impairment**
  8. Patients who are pregnant
  9. Patients who are enrolled in other investigational drug studies
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jonathan M Williams, PhD 6158759200 jon.williams@vumc.org
Contact: Jana K Shirey-Rice, PhD 6153227022 jana.shirey@vumc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03527472
Other Study ID Numbers  ICMJE 180256
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Leslie Crofford, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Kleberg Foundation
Investigators  ICMJE
Principal Investigator: Leslie J Crofford, MD Professor of Medicine - Rheumatology
PRS Account Vanderbilt University Medical Center
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP