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

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

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.

Study Overview

• Status: Completed
• Conditions: Photosensitivity
• Intervention / Treatment: Drug: Hydrochlorothiazide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Saarland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Intake of HCT 25 mg, 1 tablet/d for 15 days	Drug: Hydrochlorothiazide; Please see arm descriptions; Other Names: HCT
Placebo Comparator: Placebo; Intake of Placebo, 1 tablet/d for 15 days	Drug: Placebo; Please see arm descriptions

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in electrolytes (Na+, K+)	Changes from Baseline Visit to Day 24	26 days
Changes in kidney function (eGFR)	Changes from Baseline Visit to Day 24	26 days
Changes in blood count	Changes from Baseline Visit to Day 24	26 days

Collaborators and Investigators

• Sponsor: Universität des Saarlandes

Publications and helpful links

Helpful Links

• Hydrochlorothiazid - Risiko von nichtmelanozytärem Hautkrebs [Basalzellkarzinom (Basaliom); Plattenepithelkarzinom der Haut (Spinaliom): Rote-Hand-Brief vom 17. Oktober 2018.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): July 22, 2021
• Study Completion (Actual): July 22, 2021

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: November 27, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Photosensitivity Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide
• Other Study ID Numbers: HCTox

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No