CystinosisEarly Phase 1NCT02533076
The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients
A Early Phase 1 study testing Challenge agent: capsaicin, Mechanical stimulation with Von Frey filaments and Temperature sensitivity measurement with Advanced Thermal Stimulation in people with Cystinosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystinosis
- What is being tested?
- Challenge agent: capsaicin, Mechanical stimulation with Von Frey filaments and Temperature sensitivity measurement with Advanced Thermal Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2014to Jul 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Centre for Clinical Pharmacology, UZ Leuven
Leuven, Vlaams-Brabant, 3000
About this study
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).
Read more
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.
- Conditions
- Cystinosis
- Being tested
- Challenge agent: capsaicin, Challenge agent: placebo, Mechanical stimulation with Von Frey filaments, Temperature sensitivity measurement with Advanced Thermal Stimulation
- Medical subject headings
- Cystinosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Challenge agent: capsaicinOther
During the study period (Day 1), in each subject 3 equally spaced (minimum distance of 4 cm) 10-mm rubber O-rings (8 mm inner diameter) will be placed on the volar surface of the forearm. The most proximal ring (i.e. at least 15 cm proximal of the wrist crease) is referred to as ring number 1; the most distal ring is referred to as ring number 3; in between is ring number 2.
In ring number 1 and 2, subjects will receive a topical dose of 1000 µg/20 µL capsaicin (single-blind). Change in dermal blood flow induced by capsaicin will be measured with Laser Doppler Imaging.
Challenge agent: placeboOther
During the study period (Day 1), in each subject 3 equally spaced (minimum distance of 4 cm) 10-mm rubber O-rings (8 mm inner diameter) will be placed on the volar surface of the forearm. The most proximal ring (i.e. at least 15 cm proximal of the wrist crease) is referred to as ring number 1; the most distal ring is referred to as ring number 3; in between is ring number 2.
In ring number 3, subjects will receive a topical dose of placebo (single-blind).Change in dermal blood flow induced by placebo will be measured with Laser Doppler Imaging.
Mechanical stimulation with Von Frey filamentsDevice
Von Frey filaments will be used to measured the mechanical detection and pain threshold of the volunteers. The Von Frey filaments will be applied on the upper capsaicin spot in sequential order. The subject will be asked to indicate when he feels the application of the Von Frey filaments and when it hurts.
Temperature sensitivity measurement with Advanced Thermal StimulationDevice
Temperature sensitivity (detection and pain threshold) will be determined using Advanced Thermal stimulation. 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 a rate of 1°C/second and the volunteer will be asked to click on a computer mouse when he feels the change in temperature and when it hurts.
| Study group | Role | What they receive |
|---|---|---|
| Cystinosis Patients | Other | Cystinosis patients Receives: Other: Challenge agent: capsaicin; Other: Challenge agent: placebo; Device: Mechanical stimulation with Von Frey filaments; Device: Temperature sensitivity measurement with Advanced Thermal Stimulation |
| Healthy volunteers | Other | Healthy volunteers Receives: Other: Challenge agent: capsaicin; Other: Challenge agent: placebo; Device: Mechanical stimulation with Von Frey filaments; Device: Temperature sensitivity measurement with Advanced Thermal Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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).
Measured: Day 1 at baseline and 10, 20, 30, 40, 50 and 60 minutes after capsaicin application
Secondary outcomes (2)
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.
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.
Measured: 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.
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.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2015 (estimated)
- Study startNov 2014
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CystinosisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02533076
- Sponsor's protocol ID
- CCP13-3302-CYST
- Status last verified
- Jul 2015
- First submitted
- 14 Jul 2015
- Last updated
- 26 Aug 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Buntinx L, Voets T, Morlion B, Vangeel L, Janssen M, Cornelissen E, Vriens J, de Hoon J, Levtchenko E. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci Rep. 2016 Oct 13;6:35395. doi: 10.1038/srep35395.
PubMed 27734949
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Functional Consequences of the CTNS-deletion for the TRPV1-receptor in Cystinosis Patients
- ClinicalTrials.gov ID
- NCT02533076
- Acronym / sponsor ID
- CCP13-3302-CYST
- Conditions
- Cystinosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 26 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cystinosis Patients | Other | Other: Challenge agent: capsaicin, Other: Challenge agent: placebo, Device: Mechanical stimulation with Von Frey filaments, Device: Temperature sensitivity measurement with Advanced Thermal StimulationCystinosis patients |
| Healthy volunteers | Other | Other: Challenge agent: capsaicin, Other: Challenge agent: placebo, Device: Mechanical stimulation with Von Frey filaments, Device: Temperature sensitivity measurement with Advanced Thermal StimulationHealthy volunteers |
Who may qualify
- Ages
- 8 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Challenge agent: capsaicinDuring the study period (Day 1), in each subject 3 equally spaced (minimum distance of 4 cm) 10-mm rubber O-rings (8 mm inner diameter) will be placed on the volar surface of the forearm. The most proximal ring (i.e. at least 15 cm proximal of the wrist crease) is referred to as ring number 1; the most distal ring is referred to as ring number 3; in between is ring number 2. In ring number 1 and 2, subjects will receive a topical dose of 1000 µg/20 µL capsaicin (single-blind). Change in dermal blood flow induced by capsaicin will be measured with Laser Doppler Imaging. | Other | Cystinosis Patients, Healthy volunteers |
| Challenge agent: placeboDuring the study period (Day 1), in each subject 3 equally spaced (minimum distance of 4 cm) 10-mm rubber O-rings (8 mm inner diameter) will be placed on the volar surface of the forearm. The most proximal ring (i.e. at least 15 cm proximal of the wrist crease) is referred to as ring number 1; the most distal ring is referred to as ring number 3; in between is ring number 2. In ring number 3, subjects will receive a topical dose of placebo (single-blind).Change in dermal blood flow induced by placebo will be measured with Laser Doppler Imaging. | Other | Cystinosis Patients, Healthy volunteers |
| Mechanical stimulation with Von Frey filamentsVon Frey filaments will be used to measured the mechanical detection and pain threshold of the volunteers. The Von Frey filaments will be applied on the upper capsaicin spot in sequential order. The subject will be asked to indicate when he feels the application of the Von Frey filaments and when it hurts. | Device | Cystinosis Patients, Healthy volunteers |
| Temperature sensitivity measurement with Advanced Thermal StimulationTemperature sensitivity (detection and pain threshold) will be determined using Advanced Thermal stimulation. 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 a rate of 1°C/second and the volunteer will be asked to click on a computer mouse when he feels the change in temperature and when it hurts. | Device | Cystinosis Patients, Healthy volunteers |
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
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).
2 secondary outcomes
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
Temperature sensitivity (detection and pain threshold), measured with Advanced Thermal stimulation and expressed in degrees Celsius.
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2015.
- Derived from this study: PubMed 27734949Buntinx L, Voets T, Morlion B, Vangeel L, Janssen M, Cornelissen E, Vriens J, de Hoon J, Levtchenko E. TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion. Sci Rep. 2016 Oct 13;6:35395. doi: 10.1038/srep35395.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Challenge agent: capsaicin, Mechanical stimulation with Von Frey filaments and Temperature sensitivity measurement with Advanced Thermal Stimulation in people with Cystinosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02533076, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2015; AzTrials last refreshed its copy on 7 Nov 2026.