Management of Recurrent and Progressive Ligneous Conjunctivitis Due to Plasminogen Deficiency. An N of One Clinical Trial of Topical Administration of Allogenic Plasma to Affected Eye
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Time to change in the size of pseudomembranous lesions by 50% or greater with topical administration of aliquoted allogenic plasma in the affected conjunctiva.
研究概览
简要总结
Congenital plasminogen deficiency causes impaired wound healing and growth of pseudomembranous lesions over multiple parts of the body. The most common lesions involve eyes and are known as Ligneous conjunctivitis. These can cause scarring of the sclera, vision loss and even blindness. These pseudomembranous lesions are recur after surgical excisions, administration of intra-ocular cyclosporine, autologous serum drops or corticosteroids.
Clinical data shows that these growths do not worsen and do not recur after administration of plasminogen (either as concentrate or as plasma) in the eyes, locally or intravenously.
As plasminogen is not available as concentrate, we are using aliquoted allogenic plasma provided by Canadian Blood Services for intra-ocular application. These will be applied to eyes multiple times a day for a period of 2 to 6 months depending on disease severity and patient response. These may be used again if ligneous conjunctivitis recurs.
The patient will be followed for a period of 2 years at least. All serious adverse events will be reported to Canadian Blood Services and Health Canada as appropriate.
详细描述
This study will enroll one patient with recurrent ligneous conjunctivitis at University of Saskatchewan, Saskatchewan Health Authority in Saskatoon.
BACKGROUND:
Congenital plasminogen deficiency is an extremely rare autosomal recessive disorder that leads to formation of extravascular fibrin rich pseudomembranes in various organ systems including central nervous system, gastrointestinal, respiratory and otopharyngeal tracts (1, 2, 3). Conjunctival involvement in the form of recurrent woody growths underneath the eyelid (ligneous conjunctivitis) is the most common manifestation (5, 6). The symptoms are most severe in infants and children, where it may lead to central nervous system (CNS) hydrocephalus, respiratory failure or blindness, depending on the organ system involved (3,4)
The conjunctival pseudomembranes recur after excision and show a poor response to topical steroids, cyclosporine, or autologous serum administration. These lesions can lead to conjunctival scarring, ptosis, loss of visual acuity and ultimately blindness5,6.
Plasminogen replacement (in the form of topical drops of plasminogen concentrate or allogenic plasma) has proven to be the most effective modality in preventing growth of these lesions and is required by most patients to prevent end organ damage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients under the age of 18 years
- •Diagnosis of plasminogen deficiency (Definition: clinical presence of pseudomembranous lesions and serum plasminogen level < 50%)
- •Ocular involvement (Ligneous Conjunctivitis) due to plasminogen deficiency
排除标准
- •Patient is 18 years or older
- •Patients with no plasminogen deficiency
- •Patients with no ocular manifestations of plasminogen deficiency
研究组 & 干预措施
Intervention arm (aliquoted plasma application into the conjunctiva)
This is the only arm of the study. The intervention is administration of aliquoted plasma provided by Canadian Blood Services in eye droppers (3 ml aliquots in 7 ml vials) in the patient's conjunctiva.
The duration of therapy can be 2 to 6 months depending on response The intra-ocular drops will be administered every 1-5 hours daily in the affected eye based on disease severity and may be repeated
干预措施: Aliquoted allogeneic donor plasma in patient's conjunctiva (Drug)
结局指标
主要结局
Time to change in the size of pseudomembranous lesions by 50% or greater with topical administration of aliquoted allogenic plasma in the affected conjunctiva.
时间窗: 24 months. This knowledge will be aggregated in the patient data collection form
The presence and size of pseudomembranous lesions on the patient's conjunctiva will be assessed via ophthalmologic examination every 2-7 days for first 2 months of topical application of aliquoted plasma in affected conjunctiva. The ophthalmologic assessment will then occur at increasing intervals based on the response of patient's ligneous conjunctivitis (pseudomembranous lesions) to this therapy. Time interval to the outcome measure (change in size of pseudomembranes) will be reported as number of days from the start of administration of aliquoted plasma.
Difference in the visual acuity of affected eye after topical administration of aliquoted allogenic plasma into affected conjunctiva.
时间窗: 24 months. This information will be aggregated in data collection form
The visual acuity in the affected eye will be assessed via ophthalmologic assessment using age-appropriate measures before intervention and on a periodic basis after the start of intervention. The difference in visual acuity before and after intervention will be reported as percent difference
Mean difference in the size of pseudomembranous conjunctival lesion after 2 months of local administration of aliquoted plasma (reported as mean difference and percent difference from pre-administration size of pseudomembranous lesions )
时间窗: 24 months
The size of pseudomembranous lesions will be measured before intervention and after 4 weeks of topical administration of aliquoted plasma in patient's conjunctiva (with/without surgical excision) 8 weeks of topical administration of plasma (with/without surgical excision). This size will be compared to the size of pseudomembranes prior to intervention. The results will be reported as mean difference and percent.
Number of participants with development of strabismus or other visual defects in affected eye
时间窗: 24 months. Information will be aggregated in data collection form
Assessed via clinical ophthalmologic assessment on a periodic basis after start of administration of aliquoted plasma in patient's conjunctiva
次要结局
- Number of participants with recurrence of pseudomembranous lesions(24 months)
- Time to development of recurrence of pseudomembranous lesions in the eye undergoing intervention.(24 months)
研究者
Sarah Tehseen
Principle Investigator, Assistant Professor of Pediatric Hematology and transfusion medicine
University of Saskatchewan