Combining Lovastatin and a Parent-Implemented Language Intervention in a Multimodal Treatment for Fragile X Syndrome
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Expressive Language Sample Composite Score in the Home
研究概览
简要总结
The purpose of the study is to test the efficacy of a 20 week multi-modal treatment comprised of lovastatin or placebo, and the Parent-implemented Language Intervention (PILI) in children with fragile X syndrome (FXS). Children will be randomized to drug or placebo in a double-blind design with all participating in the PILI. The primary endpoint will be to measure improvements in spoken language and behavior among lovastatin-treated than placebo treated participants.
详细描述
This is the first multi-modal treatment to combine a targeted treatment for FXS, lovastatin, with an innovative parent-implemented intervention (PILI) targeting language and challenging behavior delivered through telehealth technology.The hypothesis is that targeted treatments will be more effective when applied in combination with PILI. Examination of whether changes in the activity of key pathways/proteins influenced by fragile X mental retardation protein (FMRP) (the mitogen-activated protein kinase (ERK) and MMP-9) are biomarkers of treatment responsiveness. Because lovastatin is also an anti-inflammatory, characterization of MEK/ERK signaling in peripheral immune cells both pre- and post- treatment will be carried out to determine whether levels of these signaling molecules are predictive biomarkers of treatment response. It is hypothesized that those individuals with elevated inflammatory cytokine profiles will be most responsive to lovastatin treatment. Once modeled in FXS, results from these studies can then be applied to other neurodevelopmental disorders including RASopathies.
The behavioral component of the proposed multi-modal treatment will be a Parent-implemented Intervention (PILI) that targets improvements in spoken language and challenging behavior for 10- to 17-year-olds with FXS by increasing parental verbal responsiveness (PVR) within picture-book based story-telling episodes. Parents will be encouraged to use the targeted strategies in other everyday interactions with their child. The intervention will be delivered to parents in their homes by way of video teleconferencing (VTC). Participants will be randomly assigned to receive the behavioral intervention alone or in combination with Lovastatin.
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
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of a full mutation with absence or deficient FMRP levels.
- •Males and females ages 10 through 17 years
- •Willingness of potential study participant as well as a parent or caretaker to participate in the protocol.
- •Speech is the primary means of communication with three-word or longer utterances used on a daily basis.
- •Intelligence quotient (IQ) ≤70 as measured by the Leiter- R.
- •Sexually active women of childbearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative qualitative serum β-human chorionic growth hormone (β-HCG) or urine pregnancy test collected at the initial screening visit.
排除标准
- •Persons who do not speak English.
- •Changes in any medications (including investigational medications) within the last month (4 weeks). All concomitant medications must have been on a stable course for at least 4 weeks prior to enrollment into the study and maintain stability throughout the course of the study.
- •Changes in behavioral therapy or educational programming during the study. This does not include scheduled school holidays.
- •Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
- •Patients who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study or displaying clinically significant abnormalities in safety assessments at screening.
- •Patients on prohibited medications
- •History of recurrent status epilepticus.
- •Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial.
- •Subjects unwilling to abstain from alcoholic beverages during the trial.
- •Subjects who are actively suicidal.
研究组 & 干预措施
Lovastatin and PILI
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with study medication Lovastatin.
干预措施: Lovastatin (Drug)
Placebo and PILI
Subjects will receive the Parent Implemented Language Intervention (PILI) in combination with placebo.
干预措施: Placebo (Other)
结局指标
主要结局
Expressive Language Sample Composite Score in the Home
时间窗: 20 weeks
The primary outcome reflects the diversity of vocabulary used. Higher scores reflect more skill. The lowest possible value is zero. No theoretical maximum can be defined because the wordless picture books can lead to a large and indeterminate set of options for the amount of talk and the vocabulary used. In a previous study of a nonpharmacological intervention, the range at baseline was 9-177, and at post-treatment, the range for the combined treated and nontreated groups was 23-214, although these values were not corrected for the number of C-units produced (McDuffie at el. 2018 Developmental Neurorehabilitation).
次要结局
- Clinical Global Impression-Improvement (CGI-I) Scale(20 weeks)
- Visual Analog Scale (VAS) - Spoken Language Impairment(20 weeks)
- Clinical Global Impression- Severity (CGI-S)(Baseline)
- Visual Analog Scale (VAS) - Social Impairment(20-weeks)
- FXS- Normed Aberrant Behavior Checklist (ABC) Social Avoidance Subscale(20 weeks)