The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Change from baseline of the dermal blood flow response to topical applied capsaicin at 10, 20, 30, 40, 50 and 60 minutes, measured with Laser Doppler Imaging and expressed in % change to baseline
研究概览
简要总结
Cystinosis is a rare autosomal recessive disorder, characterized by the abnormal accumulation of cystine in the lysosomes. Cystinosis is mostly caused by mutations in the cystinosin gene (CTNS). The major mutation, which is present in almost 50% of the cystinosis patients, is a 57-kb deletion. This deletion removes the first 9 exons and a part of exon 10 of the CTNS gene. Exon 10 of the CTNS gene is a upstream 5' region that encodes for the CARKL gene and also for the first two noncoding exons of the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) gene.
TRPV1 belongs to the transient receptor potential (TRP) superfamily of cation channels. TRPV1 is primarily expressed in sensory nerves and is activated by heating (>43°C) and a wide range of chemical stimuli. One of these chemical stimuli is capsaicin, the pungent ingredient in hot chilli peppers. The effect of binding of the exogenous ligand capsaicin with the TRPV1 receptor is well known to provoke the release of a number of bioactive substances including calcitonin gene-related peptide (CGRP). These substances, in turn, act on target cells in the surrounding tissue such as mast cells, immune cells and vascular smooth muscle cells. The resulting response is characterized by redness and warmth (secondary to vasodilatation), swelling (secondary to plasma extravasation) and allodynia (i.e. hypersensitivity to heat and touch secondary to alterations in the excitability of primary sensory neurons).
The present study wants to test the following hypotheses:
(i) The DBF response to topical applied capsaicin is decreased in cystinosis patients, compared to matched control subjects.
(ii) The skin sensitivity response after topical applied capsaicin is decreased in cystinosis patients, compared to matched control subjects.
(iii) The temperature sensitivity is decreased in cystinosis patients, compared to matched control subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Only healthy controls: Subject is in good health, based on medical history and physical examination
- •White (Caucasian) male or female subjects, aged > or = 8 year.
- •Subject is capable and willing to give informed consent.
排除标准
- •Any abnormality of the skin which may interfere with the study assessments.
- •Excessive hair growth on the volar surface of the forearm.
- •Excessive tanning (any exposure to sunlight or a tanning bed which would cause a sunburn reaction) throughout the study and incapable to cover the forearms for 24 hours prior to the study period.
- •Subject using topical treatments on the forearm.
- •History of sensitivity to the fruits of capsicum plants (e.g. chilli peppers).
- •Any situation that can compromise the study, including a predictable lack of cooperation from the volunteer.
- •Female subject is pregnant or breastfeeding.
结局指标
主要结局
Change from baseline of the dermal blood flow response to topical applied capsaicin at 10, 20, 30, 40, 50 and 60 minutes, measured with Laser Doppler Imaging and expressed in % change to baseline
时间窗: Day 1 at baseline and 10, 20, 30, 40, 50 and 60 minutes after capsaicin application
At baseline and every 10 minutes during 60 minutes after capsaicin application. DBF measurement will be done using a Laser Doppler scanner (PIM III Perimed).
次要结局
- Change from baseline of the skin sensitivity response after topical applied capsaicin at 10, 20, 30, 40, 50 and 60 minutes, measured with the Numerical rating scale and skin sensitivity to mechanical stimulation, measured with Von Frey filaments.(Day 1 at baseline and 10, 20, 30, 40, 50 and 60 minutes after capsaicin application)
- Temperature sensitivity (detection and pain threshold), measured with Advanced Thermal stimulation and expressed in degrees Celsius.(Day 1)