A Phase II, Mono-center, Placebo-controlled, Double-blind, Crossover Trial to Investigate Effect and Efficacy of Pyridostigmine in Dutch Patients With Spinal Muscular Atrophy Types 2, 3 and 4
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- UMC Utrecht
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- repeated nine-hole peg test performance
研究概览
简要总结
A trial investigating the effects of pyridostigmine (mestinon) versus a placebo in a double-blind cross over trial in patients with hereditary proximal spinal muscular atrophy (SMA) types 2, 3 and 4.
详细描述
In this cross-over trial we will investigate the effects of pyridostigmine (mestinon) versus a placebo on fatigability in patients with hereditary proximal spinal muscular atrophy (SMA) types 2, 3 and 4 (aged 12 and older) The study participants will be using a placebo during 8 weeks and mestinon during 8 weeks. Both investigators and patients are blinded to the treatment allocation in both periods. Patients will be randomly assigned to use placebo or mestinon first. At the end of the study, patients will have used both mestinon and a placebo during 8 weeks.
In both phases (periods) of the cross over study, study medication dosage will slowly be increased to a maximum dosage of 6 mg/kg/day (spread over 4 doses daily) in order to either prevent side effects or to manage them as good as possible. This scheme allows us to assist our participants in case side effects do occur early. Although we strive to have all patients on the same dosage per kg of body weight, serious side effects will obviously lead to lowering the dosage.
Before the start of medication use (either placebo or pyridostigmine), baseline measurements will be taken: a physical examination and data concerning both primary and secondary outcomes (MFM, MRC scores, fatigability tests, etc.) will be collected. After use a drug (mestinon/placebo) for 8 weeks these tests will be repeated, to evaluate possible medication effect. After a wash-out period of approximately 1-2 weeks the same scheme is used for the second study period (i.e. the cross-over design). Unblinding follows after the entire study is completed (i.e.: last included patients finishes participation).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A clinical diagnosis of SMA type 2, 3a, 3b or 4
- •Genetically confirmed homozygous SMN1 deletion
- •Ability to complete visits during trial period;
- •Given oral and written informed consent when ≥18 years old;
- •Given informed consent by the parents or legal representative(s) in case of patients aged ≥12 till <18 years old (in accordance with Dutch law)
- •Ability of performing at least 2 subsequent rounds of the Nine Hole Peg test
- •A maximum total Motor Function Measure (MFM) score of 80% (i.e.: a maximum score under 80% of the D1+D2+D3 subscores).
排除标准
- •Known concomitant disorders of the NMJ (e.g. but not limited to: Lambert Eaton myasthenic syndrome, myasthenia gravis);
- •Use of drugs that may alter NMJ function
- •Classic SMA type 1;
- •Apprehension against participation in EMG;
- •Inability to meet study visits;
- •Mechanical gastro-intestinal, urinary or biliary obstruction;
- •Clinical significant alterations of laboratory tests (electrolytes, liver function, kidney function, thyroid function or blood dysplasia) drawn within 14 days prior to start of study entry;
- •ECG abnormalities known as a contraindication for pyridostigmine use;
- •Current pregnancy or breast-feeding
- •Allergy to bromides
- •Severe bronchial asthma (in case of uncertainty of diagnosis, we will contact treating pulmonologist or physician)
- •Total MFM score at baseline (screening) > 80% (i.e.: a maximum total MFM score above 80% of the D1+D2+D3 subscores).
研究组 & 干预措施
Pyridostigmine
(this is a cross-over trial, in which participants will receive both a placebo and pyridostigmine in different study periods. Both investigators and participants are blinded for what medication is used in what period. All patients will eventually use a placebo for 8 weeks and pyridostigmine for 8 weeks).
干预措施: Pyridostigmine (Drug)
Placebo
(this is a cross-over trial, in which participants will receive both a placebo and pyridostigmine in different study periods. Both investigators and participants are blinded for what medication is used in what period. All patients will eventually use a placebo for 8 weeks and pyridostigmine for 8 weeks).
干预措施: Placebo (Drug)
结局指标
主要结局
repeated nine-hole peg test performance
时间窗: Change in performance (in time to complete) the test rounds over the course of 8 weeks of medication compared to baseline
The time needed tot complete multiple rounds of the nine hole peg test (hence: repeated NHPT) will be recorded (visit 1) and compared to the performance on the test after 8 weeks of treatment (placebo or mestinon) (visit 2). Visit 3 will serve as the baseline measurement for the 2nd study period (again followed by 8 weeks of treatment and the final study visit (visit 4)).
MFM (Motor Function Measurement).
时间窗: change over the course of 8 weeks compared to baseline
D1+D2+D3 but also D1, D2, or D3 sub scores of the MFM scales will be used.
次要结局
- endurance nine hole peg test(Change in performance after 8 weeks of therapy (placebo or mestinon).)
- endurance box-and-block test(Change in performance after 8 weeks of therapy (placebo or mestinon))
- endurance walk test(Change in performance after 8 weeks of therapy (placebo or mestinon).)