Study to Evaluate the Influence of Hydrochlorothiazide on Dermal Photosensitivity and DNA Stability - a Pilot Study (HCTox Study)

Study Overview
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Brief Summary
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The clinical trial is designed as a national, prospective, single-center, double-blind, parallel group, randomized, controlled, interventional trial to investigate whether a therapy with HCT compared with placebo can affect dermal photosensitivity and DNA stability.

Detailed Description
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Previously published retrospective analyses leading to the official warning about the use of hydrochlorothiazide (HCT). The underlying pilot study examins, if the intake of HCT leads to increased dermal photosensitivity and in combination with UV-exposition to a DNA-damage of the skin. Up until today, there is no prospective, randomized, placebo-controlled trial investigating the impact of HCT on dermal photosensitivity in greater detail. The pilot trial is designed as feasibility study to clarify the impact of HCT on dermal photosensitivity. This may facilitate evidence-based recommendations as to whether or not HCT increases the risk for skin cancer. Of note, HCT is one of most frequently prescribed drugs in Germany.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Influence of Hydrochlorothiazide on Dermal Photosensitivity and DNA Stability - a Pilot Study (HCTox Study)

Conditions
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Photosensitivity

Intervention / Treatment
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* Drug: Hydrochlorothiazide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is willing and able to participate and provides written informed consent; Healthy subjects with no concomitant medical conditions; Age ≥ 18 years; The subject is willing to take HCT 25 mg a day although not clinically indicated; The subject is willing to undergo controlled UV-exposition although not clinically indicated; Skin type I - IV. Exclusion Criteria: History of any cardiac disease; History of any dermatologic disease; Renal insufficiency (eGFR <60 ml/min/1.73m²); Intake of photosensitive substances, especially intake of HCT; Frequent, above-average, UV exposition (naturally or artificially); Known hypertension; Known electrolyte disbalance; Systolic blood pressure at baseline <100 mmHg; Skin type V and VI; History of severe diseases, which could endanger the safety of study participant; Known unresolved history of alcohol dependency or drug abuse or any other kind of dependencies Intake of any of the following medications or substances: Betablockers; nitrates; barbiturates; phenothiazines; tricyclic antidepressants; vasodilatory drugs; ACE-inhibitors; NSAIDs; salicylates; phenytoin; Insulin; oral antidiabetic drugs; vasoconstrictors; glycosides; substances lowering blood-urea levels; substances causing a Long-QT-Syndrome; chinidine; carbamazepine; cyclosporine; cholecalciferol; potassium salts; amantadine; allopurinol; methyldopa; cholestyramine; colestipol; other diuretics; lithium; cytostatic drugs; Women in childbearing age and not using medically acceptable effective contraception refer to CTFG: The study population includes female of childbearing potential. Female of childbearing potential have to agree to comply with the applicable contraceptive requirements of the protocol for the duration of the study or having post-menopausal status or be permanently sterilized (at least 6 weeks post-sterilization). Highly effective contraception is defined as a contraceptive method with failure rate of less than 1 % per year when used consistently and correctly and when applicable, in accordance with the product label; Subject is pregnant (e.g., positive ß-hCG test) or is breast feeding; Hypersensitivity to the active substance, to HCT or any of its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: National, prospective, single-center, double-blind, parallel group, randomized, controlled, interventional Trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intake of HCT 25 mg, 1 tablet/d for 15 days | Drug: Hydrochlorothiazide<br>* Please see arm descriptions<br>* Other names: HCT;|
| Placebo Comparator: Placebo<br>Intake of Placebo, 1 tablet/d for 15 days | Drug: Placebo<br>* Please see arm descriptions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in subjects´ minimal-erythema-dose (MED). | The MED is the minimal erythema dose, meaning the minimal dose of energy (in this case provided by UV-exposition) per area that leads to a clinically visible skin reaction, mainly a slight reddening. The MED is assessed by a clinical tool called the light-stair. | 2 weeks | 
| Amount of excretion of pyrimidine-dimers (PD) in urine. | Changes from Baseline Visit to Day 26 | 26 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood-serum vitamin-D levels. | Changes from Baseline Visit to Day 24 | 26 days | 
| Changes in blood pressure. | Changes from Baseline Visit to Day 24 | 26 days |