Histidine Therapy: A Project to Treat HARS Deficiency
关键词
抽象
描述
HARS syndrome is a progressive degenerative disease affecting eyesight and hearing caused by a mutation in the HARS gene which codes for an enzyme involved in protein synthesis. HARS syndrome has been exclusively found in the Old Order Amish communities in Southwestern Ontario and in Pennsylvania. Children with this disorder initially have normal vision and hearing, but with a febrile illness, can have a sudden loss of vision and hearing, as well as visual hallucinations. There is some evidence that vision loss progresses, albeit at a slower rate, even without a febrile incident. In more severe cases, fluid accumulates in the lungs (acute respiratory distress syndrome or ARDS) which can cause a drop in oxygen levels and sometimes death. There is currently no specific treatment for HARS syndrome, apart from supportive care. Anecdotal evidence of an adult with HARS syndrome who was treated with the amino acid L-histidine suggests that there was an improvement in vision, however there were no baseline objective measurements of vision prior to the use of histidine. We have designed a pilot project in which histidine will be given to children with HARS for 6 months. Investigators hypothesize that the histidine will be well tolerated and easily administered, without side effects. Investigators will monitor vision, hearing and bloodwork to determine if there is any change during the course of treatment. As well, investigators plan to administer increased doses of histidine during acute illnesses, hoping to prevent deterioration in breathing due to ARDS. The results of this initial pilot project may pave the way for a longer term study of the use of histidine.
日期
最后验证: | 02/28/2018 |
首次提交: | 09/15/2016 |
提交的预估入学人数: | 10/02/2016 |
首次发布: | 10/04/2016 |
上次提交的更新: | 08/21/2018 |
最近更新发布: | 08/23/2018 |
实际学习开始日期: | 07/31/2018 |
预计主要完成日期: | 03/31/2020 |
预计完成日期: | 03/31/2020 |
状况或疾病
干预/治疗
Dietary Supplement: Treatment
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: Treatment L-Histidine in 500mg capsules taken at a dose of 50mg/kg to maintain high-normal serum histidine levels | Dietary Supplement: Treatment L-Histidine in 500mg capsules taken at a dose of 50mg/kg to maintain high-normal serum histidine levels |
资格标准
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Have molecularly confirmed HARS syndrome (Y454S homozygous). 2. Capable of giving informed consent or assent, or have an acceptable surrogate capable of giving consent on the participant's behalf. 3. Participant or surrogate decision maker is able to understand the study procedures and comply with them throughout the course of the study. 4. Able to take solid foods (ie applesauce) or swallow capsules (in younger children, capsule may be broken and contents mixed with applesauce). 5. At least 1 year of age or greater than 8 kg in weight (since histidine is supplied as a minimal dose of 500 mg/capsule. Exclusion Criteria: 1. Unable or unwilling to give informed consent. 2. Unable to understand instructions or unable to attend clinic visits. 3. Children less than 1 year of age or less than ~8kg in weight (since histidine is supplied as 500 mg capsules). |
结果
主要结果指标
1. Visual acuity maintenance or improvement [2 years]
2. Visual acuity maintenance or improvement [2 years]
3. Visual acuity maintenance or improvement [2 years]
4. Auditory ability maintenance or improvement [2 years]
5. Auditory ability maintenance or improvement [2 years]
6. Auditory ability maintenance or improvement [2 years]
7. Auditory ability maintenance or improvement [2 years]
8. Changes in severity of acute febrile illness [2 years]
9. Changes in severity of acute febrile illness [2 years]
10. Changes in severity of acute febrile illness [2 years]
次要成果指标
1. Biomarker Changes [2 years]
2. Plasma level maintenance [1 month]