Clinical Trial: The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients

Brief Summary:

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

Detailed Summary:
Sponsor: Universitaire Ziekenhuizen Leuven

Current Primary Outcome: 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 [ Time Frame: Day 1 at baseline and 10, 20, 30, 40, 50 and 60 minutes after capsaicin application ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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. [ Time Frame: 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, skin sensitivity to capsaicin will be measured using the Numerical rating scale (NRS) -11. Skin sensitivity to mechanical stimulation will be tested using Von Frey filaments after DBF measurements are performed.
• Temperature sensitivity (detection and pain threshold), measured with Advanced Thermal stimulation and expressed in degrees Celsius. [ Time Frame: Day 1 ]
  Temperature sensitivity will be measured using Advanced Thermal stimulation (ATS) ( Pathway ATS Medoc) after DBF measurements are performed. A thermode will be attached to the hand of the volunteer with a baseline temperature of 32°C. The thermode will heat up and cool down with 1°C/second and the volunteers will be asked to click on a computer mouse when he/she detects the change in temperature and when it hurts.

Original Secondary Outcome: Same as current

Information By: Universitaire Ziekenhuizen Leuven

Dates:
Date Received: July 14, 2015
Date Started: November 2014
Date Completion:
Last Updated: August 21, 2015
Last Verified: July 2015