Clinical trial NCT03831646: Clinical, Psychological and Genetic Characteristics in Dermatological Patients
Official title: Clinical, Psychological and Genetic Characteristics of Patients With Atopic Dermatitis and Psoriasis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atopic Dermatitis
Psoriasis
Keywords: atopic dermatitis
psoriasis
brain-derived neurotrophic factor
depression
gender
immunoglobulin E
cortisol
testosterone
Lead sponsor: Astana Medical University
Sponsor class: OTHER
Collaborators: name: Ariel University
name: Tirat Carmel Mental Health Center
name: Medical Centre Hospital of the President's Affairs Administration, Republic of Kazakhstan
First posted: 2019-02-06
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Atopic dermatitis and psorisis patiens older than 18 years with mild and moderate forms of disease, and healthy volunteers

Brief summary: Atopic dermatitis (AD) and psoriasis (PS) are chronic, relapsing dermatological disorders with a high rate of psychiatric co-morbid pathology represented with depression. Brain Derived Neurotrophic Factor (BDNF) belongs to the neurotrophin family and widely studied in pathophysiology of psychiatric and dermatological disorders. A biological stress response system by altered hypothalamic-pituitary-adrenal (HPA) axis as well hypothalamic-pituitary-gonadal (HPG) axis may contribute to dermatoses and psychiatric disorders development. Various factors including gender, genetic, psychological stress, socioeconomic factors also affect the course of dermatoses.

A 10-week, case-control study evaluate clinical, psychological and biochemical parameters in AD and PS patients, and healthy control volunteers (HC) depending on gender and BDNF rs6265 gene polymorphism. All parameters are evaluated twice: at disease exacerbation (study baseline) and week 10.

The following methods are conducted: assessment of dermatological status, using Scoring of Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI); assessment of depression and anxiety according to DSM-V criteria and with Hamilton Depression Rating Scale (HAM-D) and with Hamilton Anxiety Rating Scale (HAM-A); analysis of serum BDNF (ng/ml), cortisol (nmol/L), testosterone (ng/dL) and IgE levels (IU/ml, AD only); DNA extraction and genotyping of BDNF variants.The study will last during 4-5 months.

Detailed description: Atopic dermatitis (AD) and psoriasis (PS) are related to psychodermatological disorders with chronic relapsing course, multifactorial etiology and complex pathogenesis. In accordance with DSM-V, AD and PS belong to psychosomatic disorders with psychogenic manifestation and exacerbation, whereas depression represents a high range of psychiatric co-morbid pathology in AD and PS patients. Brain Derived Neurotrophic Factor (BDNF) is a prominent representative of the neurotrophins family, widely studied in pathophysiology of psychiatric and dermatological disorders. Various factors including ethnicity, gender, genetic and socioeconomic causes as well methods of diagnosis and case definition may affect the course of dermatoses. A possible mechanism that contributes to dermatitis and psychiatric disorders development is dysregulation of the biological stress response system by altered hypothalamic-pituitary-adrenal (HPA) axis functioning. In addition many studies emphasize the role of gonadal hormones both in depression and dermatoses.

This study evaluate clinical, psychological and biochemical parameters in AD and PS patients depending on gender and BDNF rs6265 gene polymorphism. Investigators conduct a 10-week, case-control study among AD and PS patients and healthy controls (HC) volunteers. All parameters are evaluated twice: at disease exacerbation (study baseline) and week 10.

The following methods are used: assessment of dermatological status, using Scoring of Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI); assessment of depression and anxiety according to DSM-V criteria and with Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A); analysis of serum BDNF (ng/ml), cortisol (nmol/L), testosterone (ng/dL) and IgE levels (IU/ml, AD only); DNA extraction and genotyping of BDNF variants.

Sample collection and processing: blood are taken between 8-10 a.m. to prevent daily variations on week 0 and week 10 and collected to serum-separation tubes (SST) and EDTA tubes (for DNA extraction); samples are cooled (1 hr, 4°C) and centrifuged (2000xg, 10 minutes, 25°C); serum are stored at -20°C before analysis; DNA extraction from whole blood is performed≤3 days from collection and stored (-70°C).

After written informed consent and first blood sample, patients are provided with conventional treatments. For AD this include antihistamines (e.g., diphenhydramine, desloratadine), topical corticosteroids (e.g., betamethasone, mometasone) up to 3 weeks and emollients up to 2 months; for PS we will prescribe antihistamines (e.g., diphenhydramine, desloratadine), topical corticosteroids (e.g., betamethasone, mometasone) up to 3 weeks and keratolytics (2% salicylic ointment) up to 2 weeks. Patients are not prescribed antidepressants and other psychotropic agents.

For assessment of study parameters all patients and HC will be divided into subgroups according to gender (males, femaes) and BDNF gene polymorphism (Val/Val; Val/Met; Met/Met). Additionally AD patients will be divided by IgE sensitization: EAD (extrinsic, IgE sensitive) and IAD (intrinsic, IgE non-sensitive).

The study will last for 4-5 months. Patients inclusion criteria: no pregnancy; no unstable non-dermatological medical conditions, no systemic therapy (glucocorticosteroids, immunosuppressants and psychotropic drugs) within the month prior the study and blood sampling, no history of mental or other dermatological disorders, no severe forms of AD and PS; good general physical health. Inclusion criteria for HC are no pregnancy and good general physical health.

Statistics will be performed using unpaired t-test or paired t-test (week 0: week 10 comparisons, verified by Pearson/Spearman correlation). Unpaired, one-way ANOVA and/or two-way ANOVA test will be used for multiple group comparisons. Data will be presented as mean±SEM.

Eligibility criteria: Inclusion Criteria:

* mild and moderate atopic dermatitis and psoriasis
* age of patients over 18 years
* no systemic therapy (glucocorticosteroids, immunosuppressants and psychotropic drugs) within the month prior the study and blood sampling
* no history of mental or other dermatological disorders
* no unstable non-dermatological medical conditions
* good general physical health
* no pregnancy

Exclusion Criteria:

* pregnancy
* unstable non-dermatological medical conditions
* severe forms of AD and PS

Primary outcomes:
measure: Assessment of change in the severity of atopic dermatitis after conventional treatment from study onset (baseline) at week 10
timeFrame: At disease onset (study baseline) and at week 10
measure: Assessment of change in the severity of psoriasis after conventional treatment from study onset (baseline) at week 10
timeFrame: At disease onset (study baseline) and at week 10
measure: Assessment of change in the severity of depression in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10
timeFrame: At disease onset (study baseline) and week 10
measure: Assessment of the severity of depression in healthy controls (HC)
timeFrame: At disease onset (study baseline)
measure: Assessment of change in the severity of anxiety in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10
timeFrame: At disease onset (study baseline) and week 10
measure: Assessment of the severity of anxiety in HC
timeFrame: At disease onset (study baseline)
measure: Evaluation of changes in serum immunoglobulin E (IgE, IU/ml) levels from study onset (baseline) at week 10 in atopic dermatitis patients
timeFrame: At disease onset (study baseline) and week 10
measure: Analysis of serum IgE (IU/ml) levels in HC
timeFrame: At disease onset (study baseline)
measure: Evaluation of changes in serum Brain Derived Neurotrophic Factor (BDNF, ng/ml) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients
timeFrame: At disease onset (study baseline) and week 10
measure: Analysis of serum BDNF (ng/ml) levels in HC
timeFrame: At disease onset (study baseline)
measure: Evaluation of changes in cortisol (nmol/L) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients
timeFrame: At disease onset (study baseline) and week 10
measure: Analysis of serum cortisol (nmol/L) levels in HC
timeFrame: At disease onset (study baseline)
measure: Evaluation of changes in testosterone (ng/dL) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients
timeFrame: At disease onset (study baseline) and week 10
measure: Analysis of serum testosterone (ng/dL) levels in HC
timeFrame: At disease onset (study baseline)
measure: DNA extraction in AD, PS and HC
timeFrame: At disease onset (study baseline)
Secondary outcomes:
measure: Assessment and comparison (Unpaired t-test) of SCORAD scores in extrinsic atopic dermatitis (EAD, IgE level above the normal) and intrinsic atopic dermatitis (IAD, normal IgE level) patients compared with baseline after conventional treatment at week 10
timeFrame: At disease onset (study baseline) and week 10
measure: Assessment and comparison (Unpaired t-test) of PASI scores in psoriasis patients compared with baseline after conventional treatment at week 10 in accordance with BDNF gene polymorphism (Val/Val; Val/Met;Met/Met) and gender(males, females)
timeFrame: At disease onset (study baseline) and week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-D scores in EAD, IAD, PS and HC
timeFrame: At disease onset (study baseline) and week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-A scores in EAD, IAD,PS and HC
timeFrame: At disease onset (study baseline) and week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum BDNF (ng/ml) levels in EAD, IAD,PS and HC
timeFrame: At disease onset (study baseline) and at week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum cortisol (nmol/L) levels in EAD, IAD,PS and HC
timeFrame: At disease onset (study baseline) and at week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD,PS and HC
timeFrame: At disease onset (study baseline) and at week 10
measure: Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC in accordance with BDNF rs6265 gene polymorphism and gender
timeFrame: At disease onset (study baseline) and at week 10
measure: Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of testosterone/cortisol ratio in EAD, IAD, PS and HC
timeFrame: At disease onset (study baseline) and at week 10
measure: Correlation analysis of studied parameters in dermatological patients and HC
timeFrame: At disease onset (study baseline) and week 10
Other outcomes:
Locations:
city: Astana
country: Kazakhstan
facility: Tatyana Vinnik
Study officials:
affiliation: Astana Medical University
name: Tatyana Vinnik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: