Investigator initiated clinical trial of dantrolene as a treatment for Darier disease

Phase 2

Not yet recruiting

Conditions: Darier disease

Registration Number: 2024-519201-36-00

Lead Sponsor: Karolinska University Hospital

Brief Summary: To evaluate if dantrolene treatment reduce skin area affected.

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

The inclusion criteria will be histopathologically verified diagnosis combined with typical skin symptoms of hyperkeratotic papules and erythema (1), or clinical symptoms combined with family history in which the relative has a histopathologically verified diagnosis (2). Specifically, we will only include patients with a Physician Global Assessment of at least 3. Written consent to participate in the study will also be an inclusion criterion as well as age at least 18 years.

Exclusion Criteria

Liver disease including steatosis, cirrhosis and hepatitis B/C (contraindication)

Heart failure

Pulmonary disease such as COPD (but not common asthma)

Abnormal blood chemistry (assessed by blood samples)

Known or suspected allergies against dantrolene or vehicle

Systemic treatment for Dariers disease that cannot be paused during the study (e.g. acitretin)

Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation

Participation or recent participation in a clinical study with an investigational product (within 30 days).

Concomitant Medication that may interact (taken at least bi-weekly for medications taken on a daily basis or at all for depo medications): antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine), antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone), apalutamide, benzodiazepines (e.g., alprazolam, diazepam, lorazepam), bosentan, brimonidine, buspirone, calcium channel blockers (e.g., amlodipine, diltiazem, verapamil), cannabis, chloral hydrate, dabrafenib, dexamethasone, efavirenz, enzalutamide, etravirine, methadone, mirtazapine, mitotane, modafinil, muscle relaxants (e.g., baclofen, cyclobenzaprine, methocarbamol, orphenadrine), nabilone, narcotic pain relievers (e.g., codeine, fentanyl, morphine, oxycodone), pramipexole, rifabutin, rifampin, ropinirole, rotigotine, St. John's wort, scopolamine, seizure medications (e.g., carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide), selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline), siltuximab, sodium oxybate, tapentadol, thalidomide, tocilizumab, tramadol, tricyclic antidepressants (e.g., clomipramine, desipramine, imipramine), zolpidem, zopiclone

Wheat allergy (contraindication)

Hypersensitivity to the active substance or to any filling material (contraindication)

Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (contraindication)

Whenever spasticity is utilized to obtain or maintain increased function (contraindication)

Pregnancy, breastfeeding, or planned pregnancy.

Recent acute illness (past 4 weeks)

Active substance abuse

Kidney disease

Study & Design

Study Type: Not specified

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint will be a reduction of skin area affected using the 5-point Physician Global Assessment (PGA) scale (23). A 20 % reduction (1 point) will be considered the minimal clinically important difference.		The primary endpoint will be a reduction of skin area affected using the 5-point Physician Global Assessment (PGA) scale (23). A 20 % reduction (1 point) will be considered the minimal clinically important difference.

Secondary Outcome Measures

Name	Time	Method
As the main secondary endpoint, improvement in dermatological quality of life index (DLQI) will be used. A 4 points improvement in DLQI will be considered the minimal clinically important difference (24). We will also examine mood with the Montgomery–Åsberg Depression Rating Scale (MADRS) and treatment satisfaction with the Treatment Satisfaction Questionnaire for Medication (TSQM).		As the main secondary endpoint, improvement in dermatological quality of life index (DLQI) will be used. A 4 points improvement in DLQI will be considered the minimal clinically important difference (24). We will also examine mood with the Montgomery–Åsberg Depression Rating Scale (MADRS) and treatment satisfaction with the Treatment Satisfaction Questionnaire for Medication (TSQM).
As complementary skin assessment tools we will use the Eczema Area and Severity Index (EASI) scale and Body Surface Area (BSA).		As complementary skin assessment tools we will use the Eczema Area and Severity Index (EASI) scale and Body Surface Area (BSA).
Number of adverse events and adverse reactions, serious and non-serious.		Number of adverse events and adverse reactions, serious and non-serious.

Trial Locations

Locations (1): Karolinska University Hospital
🇸🇪
Solna, Sweden
Karolinska University Hospital
🇸🇪Solna, Sweden
Jakob Wikström
Site contact
46739611019
jakob.wikstrom@ki.se