Primary objectives:• To explore whether daily oral treatment with 30 mg prednisolone modulates biomarkers for adverse metabolic effects in a similar manner in patients with chronic atopic dermatitis as compared to healthy volunteers.• To determine…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The effect of prednisolone on several metabolic parameters will be measured in
blood. Also will be studied whether the negative metabolic effects in AD
patients are modulated in the same way as in healthy subjects. In group A and B
disease activity will be assessed by a trained dermatologist.
Secondary outcome
Identification of biomarkers in blood (e.g. lymphocyte count) that reflect the
immunosuppressive/ anti-inflammatory effect of daily oral treatment with 30 mg
prednisolone in patients with chronic atopic dermatitis.
Background summary
Glucocorticoids (GCs) such as prednisolone are potent anti-inflammatory drugs
that are crucial in the treatment of many autoimmune disorders including skin
disorders like psoriasis and atopic dermatitis. Chronic use of high oral
dosages of GCs is hampered by severe adverse effects that include metabolic
changes. This can lead to a.o. induction of insulin-resistance which is
strongly associated with elevated risk for cardiovascular disease and type 2
Diabetes. A main effort within pharmaceutical industry is the development of
GCs with an increased therapeutic index; so called dissociating GCs (diss GC),
with a better therapeutic index, as effective as prednisolone but shows less
adverse reactions.
Of all indications that are treated with prednisolone, atopic dermatitis (AD)
was selected as the most ideal indication for a trial examining prednisolone
as these patients sometimes are treated with relatively high doses of oral
prednisolone for a limited period of time with good effect on disease activity.
Study objective
Primary objectives:
• To explore whether daily oral treatment with 30 mg prednisolone modulates
biomarkers for adverse metabolic effects in a similar manner in patients with
chronic atopic dermatitis as compared to healthy volunteers.
• To determine the most suitable scoring method for quantification of the
clinical effect of daily oral treatment with 30 mg prednisolone in patients
with chronic atopic dermatitis.
Secondary objectives:
• To identify biomarkers that reflect negative effects and immunosuppressive /
anti-inflammatory effects of daily oral treatment with 30 mg prednisolone in
patients with chronic atopic dermatitis.
Study design
The subjects in this trial will be divided into three treatment groups:
Group A: Twelve subjects with chronic atopic dermatitis will be treated once
daily during 15 days with 30 mg prednisolone in an open trial.
Group B: Twelve subjects with chronic atopic dermatitis will be randomized to
one of the following treatments: B1) placebo on Day 0-1 and 30 mg prednisolone
on Day 2-15 or B2) placebo on Day 0 and 30 mg prednisolone Day 1-15.
Group C: Twelve healthy volunteers will be randomized to one of the following
treatments: C1) placebo on Day 0-1 and 30 mg prednisolone on Day 2-15 or C2)
placebo on Day 0 and 30 mg prednisolone Day 1-15.
Intervention
Daily oral treatment with 30 mg prednisolone for 15 days. In group B and C
placebo can be given instead of prednisolone for a maximum of 2 days.
Study burden and risks
Prednisolone treatment (30 mg daily during 2 weeks) is a normal treatment
regime in daily practice. It is unlikely that is this period clinical
significant negative effects will occur. Normal individuals treated with 30 mg
prednisolone will show a daily decrease of lymphocytes after the administration
of the prednisolone. The decrease normalizes within 24 hrs after the
administration. A 2-week treatment with a maximum of 30 mg prednisolone per day
does not increase the infection risk. Lymphocyte numbers will however be
frequently monitored during the trial.
Information about the possible negative effects associated with prednisolone
use can be found in the information leaflet for the subjects and the product
characteristics sheet (SmPC) provided by the supplier. Subjects with a
clinically relevant medical history or current medical condition mentioned as
contraindication or special warning in case of simultaneous prednisolone use,
as mentioned in the protocol, are excluded from participation.
The total amount of blood drawn during the study will not exceed 500 ml.
PO Box 20
5340 BH Oss
Nederland
PO Box 20
5340 BH Oss
Nederland
Listed location countries
Age
Inclusion criteria
For Patients with atopic dermatitis:
1. Atopic dermatitis according to the criteria of Hanifin and Rajka (1980).
2. Having severe chronic atopic dermatitis according to the treating dermatologist, in need of oral immunosuppressant treatment.;For all subjects:
3. Male or female at the age of 18-65 years (extremes included) on the day of the first dosing. Females of child bearing potential willing to use a double barrier method of birth control (e.g. hormonal contraception or IUD in combination with a condom or a diaphragm with spermicide) unless the subject has a vasectomized partner (> 6 months) or the subject is abstinent, during the trial.
4. Have a body weight resulting in a body mass index (BMI) of 20-32 kg/m2 (extremes included).
Exclusion criteria
For Patients with atopic dermatitis:
1. Having bacterial or viral infected eczema. ;For all subjects:
2. History of familiar Diabetes type II (first line).
3. Clinically relevant history or presence of any medical disorder, potentially interfering with the trial e.g., diabetes, presence of a clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease and/or conditions needing special attention as mentioned in the Summary of Product Characteristics (SmPC) of prednisolone.
4. History of malignancy within the last five years.
5. Clinically relevant vital signs or physical findings at screening as judged by the investigator.
6. Fasting glucose level of >= 5.6 mmol/l.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-001932-30-NL |
| CCMO | NL20045.041.08 |