Does a Nasal Instillation of Miglustat Normalize the Nasal Potential Difference in Cystic Fibrosis Patients Homozygous for the F508del Mutation? A Randomized, Double Blind Placebo-controlled Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport)
研究概览
简要总结
The purpose of this study is to investigate within a short delay the effect of nasal instillation of Miglustat on nasal potential difference in cystic fibrosis patients homozygous for the F508del mutation.
详细描述
Miglustat is an inhibitor of α-glucosidases and other enzymes. Oral miglustat is currently marketed in Europa and US for the treatment of Gaucher type 1 patients for whom enzyme replacement treatment is not an option.
Gastro-intestinal side effects are common with this formulation. This medication has been shown to have a beneficial effect both on Cl- an Na+ transports in cystic fibrosis epithelial cells. In addition, a single airway delivery of low-dose Miglustat normalizes nasal potential difference (NPD) in F508del cystic fibrosis mice. NPD abnormalities specific of CF patients are considered to reflect the primary defect of CFTR protein so that any curative treatment is expected to correct them at least partially.
In the field of respiratory pharmacology, it is a general rule that the inhaled route is to be favoured whenever possible : it is usually more effective despite much lower doses and systemic absorption (which also implies lower costs and improved tolerance).
The aim of this study is to investigate the effect of a single local administration of Miglustat on NPD measurements in CF patients homozygous for the F508del mutation.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cystic fibrosis patients homozygous for the F508del mutation as confirmed by genetic test
- •Aged 14 years and older
- •Male or female (non-pregnant women who are to remain non-pregnant for 3 months after the end of the study)
- •FEV1 > 50% of predicted normal
排除标准
- •Acute respiratory tract infection or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of visit 1
- •Any condition prohibiting the correct measurement of the NPD such as respiratory tract infection
- •Active or passive smoking
- •Allergic chronic rhinitis
- •History of significant lactose intolerance
- •History of neuropathy
- •History of cataracts or known increased risk of cataract formation
- •Hypersensitivity to miglustat or any excipients
- •Planned treatment or treatment with another investigational drug or therapy within 1 month prior to randomisation
研究组 & 干预措施
Miglustat
Nasal instillation of Miglustat (visit 2 or 3)
干预措施: Miglustat (Drug)
Placebo
Nasal instillation of placebo (visit 3 or 2)
干预措施: Placebo (Drug)
结局指标
主要结局
change in response to Chloride-free solution and isoproterenol ( reflecting chloride transport)
时间窗: change from baseline ( visit 1) and placebo to miglustat instillation
次要结局
- change in basal voltage value and in amiloride response ( reflecting sodium transport)(change from baseline (visit1) and placebo to miglustat instillation)