The Role of TRP Channels in CIPN

Not Applicable

Recruiting

• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Interventions: Other: Cinnamaldehyde and capsaicin

• Registration Number: NCT04415892
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

Part I:

Evaluating the increase in dermal blood flow upon topical application of cinnamaldehyde and capsaicin on the fingers in healthy, male volunteers. In addition, the inter-period and inter-hand reproducibility of the increase in dermal blood flow will be assessed.

Part II:

Evaluating the increase in dermal blood flow upon topical application of cinnamaldehyde and capsaicin on the fingers in patients suffering from chemotherapy-induced peripheral neuropathy compared to matched healthy volunteers.

Part III:

Evaluating the increase in dermal blood flow upon topical application of cinnamaldehyde and capsaicin on the fingers in patients who are treated with paclitaxel or oxaliplatin.

Detailed Description

The primary aim is to investigate whether paclitaxel and/or oxaliplatin alter TRP channel functionality in vivo in human. TRP functionality can indirectly be assessed via dermal blood flow changes which are part of the so-called neurogenic inflammation, induced upon TRP activation. In vivo in human, TRP can be activated via topical application of cinnamaldehyde or capsaicin on the skin.

In Part I of the study, the DBF changes upon topical application of cinnamaldehyde or capsaicin on the fingers will be characterized, including inter-period and inter-hand reproducibility.

In Part II, patients who are suffering from chronic CIPN after treatment with paclitaxel or oxaliplatin are included. DBF changes upon cinnamaldehyde and capsaicin are compared to a matched control group.

In Part III, DBF changes are assessed in patients prior to the first administration of taxol/oxaliplatin and at regular points in time during the dosage regimen.

Study Timeline

• Study Start: 2019-10-01
• Study First Submitted: 2020-05-20
• Study First Submitted QC: 2020-06-02
• Study First Posted: 2020-06-04
• Status Verified: 2024-02
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-27
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

Exclusion Criteria

1. Subject has eczema, scleroderma, psoriasis, dermatitis, or keloids, tumors, ulcers, burns, flaps or grafts on their fingers or any other abnormality of the skin which, in the opinion of the investigator may interfere with the study assessments.
2. Subject has excessive hair growth on the fingers.
3. Subject cannot avoid excessive tanning (any exposure to sunlight or a tanning bed which would cause a sunburn reaction) throughout the study.
4. Subject has a history of significant severe (drug) allergies.
5. Subject uses any prescription or non-prescription drugs on a regular basis which, in the investigator's opinion, might confound the results of the study.
6. Subject currently uses lotions, oils, depilatory preparations, makeup, or other topical treatments on the fingers on a regular basis which cannot be discontinued for the duration of the study.
7. Subject is unable to refrain from drinking alcohol 24 hours prior to each study visit, is currently a regular user of any illicit drugs, or has a history of drug (including alcohol) abuse.
8. Subject is unable to refrain from drinking caffeinated beverages (e.g. coffee, tea, cola, ...) 24 hours prior to each study visit. Subject is unable to limit their intake of caffeinated beverages to ≤4 cups a day throughout the study.
9. Subject has any of the following vital sign measurements at screening after at least 10 minutes of supine rest: Heart Rate <40 or >100 beats/min, Diastolic Blood Pressure <50 or >90 mmHg, Systolic Blood Pressure <90 or >140 mmHg.
10. Subject is currently participating or has been involved in testing an investigational drug in another clinical study within the last 4 weeks.
11. Subject is in a situation or has a condition which, in the opinion of the investigator, may interfere with safe and optimal participation in the study.
12. Subject has a history of any illness or disorder which, in the investigator's opinion, might confound the results of the study.
13. Subject suffered from peripheral neuropathy prior to the chemotherapeutic treatment (Only for patients).
14. Subject has (a history of) diabetes mellitus, amyloidosis, vitamin B deficiency or any other medical disorder that, in the investigator's opinion, may cause peripheral neuropathy (only for Part II and III).
15. Subject has (a history of) a lesion in the central nervous system that is known to possibly cause neuropathic pain: e.g. spinal cord injury, infarction localized in the brainstem or thalamus, syringomyelia, multiple sclerosis, or any other disorder of the CNS that, in the investigator's opinion, may cause neuropathic pain (only for Part II and III).
16. Subject has a history of treatment with bortezomib, vincristine, or any other compound that, in the investigator's opinion, may cause neuropathic pain (only for Part II and III).
17. Subject did not develop neuropathy after treatment with epirubicine-cyclofosfamide (only for the paclitaxel group in Part III).
18. Subject has a family history of peripheral neuropathy (only for Part II and III).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paclitaxel Patients	Cinnamaldehyde and capsaicin	Group of patients after treatment with paclitaxel.
Oxaliplatin Patients	Cinnamaldehyde and capsaicin	Group of patients after treatment with oxaliplatin.
Paclitaxel Controls	Cinnamaldehyde and capsaicin	Group of healthy volunteers, matched for sex, age and BMI with the group of Paclitaxel Patients.
Oxaliplatin Controls	Cinnamaldehyde and capsaicin	Group of healthy volunteers, matched for sex, age and BMI with the group of Oxaliplatin Patients.
Healthy volunteers	Cinnamaldehyde and capsaicin	Young, healthy male volunteers to characterize the DBF changes upon cinnamaldehyde and capsaicin, including the reproducibility.
Longitudinal Paclitaxel Patients	Cinnamaldehyde and capsaicin	Group of patients who are treated with paclitaxel.
Longitudinal Oxaliplatin Patients	Cinnamaldehyde and capsaicin	Group of patients who are treated with oxaliplatin.

Primary Outcome Measures

Name	Time	Method
Inter-hand reproducibility cinnamaldehyde	Dermal blood flow response measured simultaneously on both hands during 60 minutes post-application during study visit 1	The within subject inter-hand reproducibility of the dermal blood flow response to topical application of cinnamaldehyde as assessed by LASCA on the fingers in healthy, male volunteers
DBF in patients before, during and after chemotherapeutic treatment	Dermal blood flow measured prior to the first, or within 5 days after administration of paclitaxel or oxaliplatin	The dermal blood flow changes upon topical application of cinnamaldehyde and capsaicin in patients prior to, during and after treatment with either paclitaxel or oxaliplatin.
Inter-hand reproducibility capsaicin	Dermal blood flow response measured simultaneously on both hands during 60 minutes post-application during study visit 3	The within subject inter-hand reproducibility of the dermal blood flow response to topical application of capsaicin as assessed by LASCA on the fingers in healthy, male volunteers.
Inter-period reproducibility capsaicin	Interval of at least 5 days between both periods	The within subject inter-period reproducibility (i.e. assessing changes) of the dermal blood flow response to topical application of capsaicin as assessed by LASCA on the fingers in healthy, male volunteers.
Inter-period reproducibility cinnamaldehyde	Interval of at least 5 days between both periods	The within subject inter-period reproducibility (i.e. assessing changes) of the dermal blood flow response to topical application of cinnamaldehyde as assessed by LASCA on the fingers in healthy, male volunteers
Characterization cinnamaldehyde	Dermal blood flow response measured during 60 minutes post-application	The dermal blood flow response to topical application of cinnamaldehyde as assessed by LASCA on the fingers in healthy, male volunteers.
Characterization capsaicin	Dermal blood flow response measured during 60 minutes post-application	The dermal blood flow response to topical application of capsaicin as assessed by LASCA on the fingers in healthy, male volunteers
DBF patients compared to healthy volunteers	Dermal blood flow measured in patients who are suffering from CIPN 1 to 12 months after the last administration of paclitaxel or oxaliplatin.	The dermal blood flow changes upon topical application of cinnamaldehyde and capsaicin in patients suffering from chemotherapy-induced peripheral neuropathy compared to matched healthy volunteers.

Trial Locations

Locations (1)

KU Leuven; 🇧🇪 Leuven, Vlaams-Brabant, Belgium