First Study of Oral Cysteamine in Cystic Fibrosis

• Status: Completed
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The morbidity and mortality associated with Cystic Fibrosis (CF) are the result of chronic suppurative lung disease. The aggressive use of antibiotics is one of the mainstays of treatment in CF, however, the problems of multiple drug resistance and adverse reactions are major clinical issues.

Cysteamine is a licensed drug used in the treatment of cystinosis. In vitro work suggests that cysteamine has properties of potential benefit in CF. Cysteamine is a potent mucolytic, it disrupts biofilms, it is antimicrobial, and synergises with other antibiotic agents. CF is characterised by malabsorption and it is not known whether cysteamine is absorbed in CF, furthermore it is not known if cysteamine enters the bronchial secretions. It is not possible to assume that the pharmacokinetics of cysteamine in patients with CF are the same as those reported for cystinosis.

Objectives: to characterise the pharmacokinetic profile of cysteamine in people with CF, to ascertain whether cysteamine enters the bronchial secretions and the tolerability of cysteamine by patients with CF.

Method: a single centre, single group open label investigation of the tolerability and pharmacokinetics of oral cysteamine (Cystagon) when administered to patients with Cystic Fibrosis at the dose licensed for use in cystinosis.

Setting: adult CF clinic, Aberdeen Royal Infirmary.

Target population: 12 patients aged ≥18years with CF associated lung disease who are clinically stable.

Intervention: Oral cysteamine (Cystagon) will be increased from 450mg od to 450mg qds over three weeks, they will remain on 450mg qds for two weeks.

Assessment: face to face health outcome assessments will be carried out for all participants at recruitment/baseline, 1, 2, 3, and 5 and 6 weeks. Serial blood cysteamine levels will be measured in the first 24 hours after the first dose. Sputum cysteamine will be quantified after two weeks of full dose cysteamine 450mg qds. Disease specific health status (CFQ-R) will be assessed at baseline and after two weeks of full dose. At each assessment, lung function (FEV1, FVC), adverse reactions and serious adverse events will be ascertained. Blood samples will be taken for measurement of haematological and biochemical parameters. Sputum samples at each assessment will be analysed for microbial load and spinnbarkeit.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Aberdeen
• Collaborators: Cystic Fibrosis Trust; NHS Grampian; University of Huddersfield
• Treatments: Cysteamine

Criteria

Inclusion Criteria:

• CF related suppurative lung disease who expectorate sputum,

• Clinically stable for >4 weeks,

• Aged ≥18 years,

• Weight >50kg,

• Female participants of child bearing potential should be using a reliable form of contraception.

Exclusion Criteria:

• Hypersensitivity to the active substance, any form of cysteamine, or to any of the excipients.

• Hypersensitivity to penicillamine.

• Lung, liver transplant, on active transplant list.

• For women, current pregnancy or breast-feeding, or planned pregnancy during the study.

• Any other significant disease/disorder which, in the investigator's opinion, either puts the patient at risk because of study participation or may influence the results of the study or the patient's ability to participate in the study.