Efficacy, Safety, and Tolerability of Ultra-high-caloric, Fatty Diet (UFD) in Amyotrophic Lateral Sclerosis (ALS)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 392
- 试验地点
- 23
- 主要终点
- Survival
研究概览
简要总结
This study aims at evaluating efficacy and tolerability of an ultra-high-caloric, fatty diet (UFD) compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
详细描述
ALS is a fatal neurodegenerative disease, leading to progressive paralysis of voluntarily innervated muscles and to death caused by respiratory failure after a mean disease duration of 2-4 years.The proposed study aims at improving survival of ALS patients by targeting metabolic parameters. ALS patients feature an intrinsic hypermetabolism as signified by an increased resting energy expenditure, which significantly contributes to progressive weight loss and cachexia. The extent of weight loss is an independent prognostic factor for survival in ALS. It has been shown that survival of ALS mice can be prolonged by applying a high-caloric nutrition. Furthermore, ALS patients feature distinct alterations of lipid metabolism, and various studies suggest a protective effect of high triglyceride serum levels.
In the precursor-study LIPCAL-ALS-I, a randomized, placebo-controlled, multicenter trial, evaluating the effects of a high-caloric fatty diet (HCFD), the primary endpoint (survival in the whole study population) was missed. However, post-hoc analysis revealed showed that HCFD (1) increased survival and reduced weight loss in normal to fast-progressing patients (patients with a functional decline measured by ALS Functional Rating Scale Revised) above the median at baseline; p=0.02), (2) slowed down functional decline (measured by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised) in the whole study population (p<0.0125), and (3) lowered neurofilament light chain (NfL) serum levels as a prognostic biomarker in the whole study population (p=0.0225).
Therefore, this study aims at prolonging survival in ALS patients by applying 1.5-fold dosage of the same intervention as in LIPCAL-ALS I in a larger number of patients, excluding patients with slow disease progression.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Possible, probable (clinically or laboratory supported) or definite amyotrophic lateral sclerosis according to the revised version of the El Escorial criteria
- •Disease duration (onset of first paresis or bulbar symptoms) < 24 months
- •Loss of amyotrophic lateral sclerosis functional rating scale revised of ≥ 0.33 points/month based on the formula: (48 - myotrophic lateral sclerosis functional rating scale revised score at screening visit) / (months between onset and screening visit)
- •Age ≥18 years.
- •Either continuously treated with a stable dose of riluzole, OR not treated with riluzole for the last 4 weeks prior to inclusion
- •Either continuously treated with a stable dose of edaravone, OR not treated with edaravone for the last 4 weeks prior to inclusion
- •Either continuously treated with a stable dose of sodium-phenylbutyrate/taurursodiol, OR not treated with sodium-phenylbutyrate/taurursodiol for the last 4 weeks prior to inclusion
- •Capable of thoroughly understanding all information given
- •full written informed consent according to good clinical practice
排除标准
- •Previous participation in another interventional study involving an active treatment within the preceding 4 weeks
- •Tracheostomy or continuous permanent ventilator dependence (>22 hours per day)
- •Pregnancy or breastfeeding
- •Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
- •Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment.
- •Evidence of a major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms.
- •Liable to be not cooperative or comply with study requirements as assessed by the investigator, or unable to be reached in the case of emergency
研究组 & 干预措施
Ultra-high-caloric fatty diet
ultra-high-caloric, high-fat, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +630 kcal and +70g fat per day
干预措施: Ultra-high-caloric fatty diet (Dietary Supplement)
Placebo
placebo, fluid nutritional supplement oral intake of 4 times 35 ml per day in addition to normal food intake, corresponding to +50 kcal and +3,5g fat per day
干预措施: Placebo (Other)
结局指标
主要结局
Survival
时间窗: 18 months
Time from date of randomization until date of death, tracheostomy, or permanent continous ventilation (\>22 hours per day)
次要结局
- Survival(6 months)
- Time to tracheostomy(18 months)
- Slow vital capacity(18 months)
- Time to death(18 months)
- Ventilation assistance-free survival(18 months)
- Body Mass Index(18 months)
- Neurofilament light chain(18 months)
- Neurofilament Assess Score(18 months)
- Rasch Overall Amyotrophic Lateral Sclerosis Disability Scale(18 months)
- Time to permanent continous ventilator dependence(18 month)
- Amyotrophic Lateral Sclerosis Functional Rating Scale Revised(18 months)
- Individual Quality of Life(18 months)
- Survival(12 months)
- Amyotrophic Lateral Sclerosis Functional Rating Scale Revised Prediction Model(18 months)
- Council of Nutrition Appetite Questionnaire(18 months)
- Eating Habits(18 months)
研究者
Albert Christian Ludolph, Prof.
Prof. Dr.
University of Ulm