A Randomized Placebo-controlled, Double Blind Phase 2 Clinical Trial of Memantine for the Treatment of Cognitive Impairment in Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 3
- 主要终点
- Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Memantine (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Repeatable Battery for Assessment of Neuropsychological Status (RBANS) Total Index Score at endpoint (Visit 4)
时间窗: 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.
次要结局
- Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K(12 weeks)
- RBANS Subscales(12 weeks)
- Polysymptomatic Distress Scale(12 weeks)
- Incidence of Treatment-Emergent Adverse Events(12 weeks)
- Beck Depression Inventory(12 weeks)
- Hospital Anxiety and Depression Scale(12 weeks)
- Patient Global Impression of Change(Endpoint (Visit 4))
研究者
James C. Jackson
Professor of Medicine
Vanderbilt University Medical Center