Clinical trial NCT04654312: Study to Evaluate the Influence of Hydrochlorothiazide on Dermal Photosensitivity and DNA Stability - a Pilot Study (HCTox Study)
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Influence of Hydrochlorothiazide on Dermal Photosensitivity and DNA Stability - a Pilot Study (HCTox Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Photosensitivity
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2020-12-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: National, prospective, single-center, double-blind, parallel group, randomized, controlled, interventional Trial.
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. The subject is willing and able to participate and provides written informed consent;
2. Healthy subjects with no concomitant medical conditions;
3. Age ≥ 18 years;
4. The subject is willing to take HCT 25 mg a day although not clinically indicated;
5. The subject is willing to undergo controlled UV-exposition although not clinically indicated;
6. Skin type I - IV.

Exclusion Criteria:

1. History of any cardiac disease;
2. History of any dermatologic disease;
3. Renal insufficiency (eGFR \<60 ml/min/1.73m²);
4. Intake of photosensitive substances, especially intake of HCT;
5. Frequent, above-average, UV exposition (naturally or artificially);
6. Known hypertension;
7. Known electrolyte disbalance;
8. Systolic blood pressure at baseline \<100 mmHg;
9. Skin type V and VI;
10. History of severe diseases, which could endanger the safety of study participant;
11. Known unresolved history of alcohol dependency or drug abuse or any other kind of dependencies
12. 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;
13. 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;
14. Subject is pregnant (e.g., positive ß-hCG test) or is breast feeding;
15. Hypersensitivity to the active substance, to HCT or any of its excipients.

Primary outcomes:
measure: Changes in subjects´ minimal-erythema-dose (MED).
timeFrame: 2 weeks
measure: Amount of excretion of pyrimidine-dimers (PD) in urine.
timeFrame: 26 days
Secondary outcomes:
measure: Changes in blood-serum vitamin-D levels.
timeFrame: 26 days
measure: Changes in blood pressure.
timeFrame: 26 days
Other outcomes:
measure: Changes in electrolytes (Na+, K+)
timeFrame: 26 days
measure: Changes in kidney function (eGFR)
timeFrame: 26 days
measure: Changes in blood count
timeFrame: 26 days
Locations:
city: Homburg
country: Germany
facility: Saarland University Hospital
state: Saarland
Study officials:
affiliation: Saarland University Hospital
name: Felix Mahfoud, MD
role: PRINCIPAL_INVESTIGATOR
References: