Clinical, Psychological and Genetic Characteristics of Patients With Atopic Dermatitis and Psoriasis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Assessment of change in the severity of atopic dermatitis after conventional treatment from study onset (baseline) at week 10
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •pregnancy
- •unstable non-dermatological medical conditions
- •severe forms of AD and PS
结局指标
主要结局
Assessment of change in the severity of atopic dermatitis after conventional treatment from study onset (baseline) at week 10
时间窗: At disease onset (study baseline) and at week 10
Assessment of atopic dermatitis severity is conducted using Scoring of Atopic Dermatitis (SCORAD) index. SCORAD index formula is: A/5 + 7B/2 + C. In this formula A is defined as the extent (0-100), B is defined as the intensity (0-18) and C is defined as the subjective symptoms (0-20). The maximum SCORAD score is 103. SCORAD \<23 - mild AD; SCORAD from 23 to 63 - moderate AD; SCORAD\> 63 - severe AD.
Assessment of change in the severity of psoriasis after conventional treatment from study onset (baseline) at week 10
时间窗: At disease onset (study baseline) and at week 10
Assessment of the psoriasis severity is conducted using Psoriasis Area and Severity Index (PASI). The patient's body is divided into four sections (head (H) (10% of a person's skin); arms (A) (20%); trunk (T) (30%); legs (L) (40%)). The percent of skin lesions of each area is assessed as follows: 0 (0% of involved area); 1 (\< 10%); 2 (10-29%); 3 (30-49%); 4 (50-69%); 5 (70-89%); 6 (90-100%). Further, for each region, the intensity of 3 clinical signs is evaluated - redness, thickness and scaling and assessed as follows: 0 - no lesions,1 - easy, 2 - moderate, 3 - severe, 4 - very severe. The sum of all three severity parameters is calculated for each section, multiplied by the area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 0.3 for body, 0.4 for legs). PASI range is from 0 (no disease) to 72 (maximum disease). The severity of psoriasis is assessed as follows: PASI \<20 - mild; PASI from 20 to 50 - moderate; PASI\> 50 - severe
Assessment of change in the severity of depression in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10
时间窗: At disease onset (study baseline) and week 10
Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28
Assessment of change in the severity of anxiety in atopic dermatitis and psoriasis patients after conventional treatment from study onset (baseline) at week 10
时间窗: At disease onset (study baseline) and week 10
Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe
Assessment of the severity of depression in healthy controls (HC)
时间窗: At disease onset (study baseline)
Depression is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Depression Rating Scale (HAM-D) using the following ranges: absence, ≤7; mild, 8-16; moderate, 17-27; severe, ≤28
Analysis of serum cortisol (nmol/L) levels in HC
时间窗: At disease onset (study baseline)
The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L
Assessment of the severity of anxiety in HC
时间窗: At disease onset (study baseline)
Anxiety is assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM) -V criteria and with Hamilton Anxiety Rating Scale (HAM-A) using the following ranges: ≤17, easy; 18-24, moderate; over 25, medium-severe
Evaluation of changes in serum immunoglobulin E (IgE, IU/ml) levels from study onset (baseline) at week 10 in atopic dermatitis patients
时间窗: At disease onset (study baseline) and week 10
The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml
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
时间窗: At disease onset (study baseline) and week 10
Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used
Analysis of serum BDNF (ng/ml) levels in HC
时间窗: At disease onset (study baseline)
Serum BDNF levels are analyzed using a solid-phase, sandwich, two-site, ELISA (Promega, US; G7610). No measurement scale is used
Evaluation of changes in testosterone (ng/dL) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients
时间窗: At disease onset (study baseline) and week 10
The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.
Analysis of serum testosterone (ng/dL) levels in HC
时间窗: At disease onset (study baseline)
The total testosterone levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: men 20-49 years - 72 -853ng/dL; men≥50 years -129-767 ng/dL; women ovulating - 0.010-73.0 ng/dL; women postmenopausal - 0.010-43.0 ng/dL.
DNA extraction in AD, PS and HC
时间窗: At disease onset (study baseline)
DNA extraction and genotyping the BDNF rs6265 (Val66Met) gene polymorphism in AD, PS and HC
Analysis of serum IgE (IU/ml) levels in HC
时间窗: At disease onset (study baseline)
The total IgE levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 0.000-100.0 IU/ml
Evaluation of changes in cortisol (nmol/L) levels from study onset (baseline) at week 10 in atopic dermatitis and psoriasis patients
时间窗: At disease onset (study baseline) and week 10
The total cortisol levels are detected using solid-phase, chemiluminescent immunometric assay in an Immulite/Immulite 1000 (Siemens, Germany). Normal ranges are as follow: 138-690 nmol/L
次要结局
- 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)(At disease onset (study baseline) and week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-D scores in EAD, IAD, PS and HC(At disease onset (study baseline) and week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum cortisol (nmol/L) levels in EAD, IAD,PS and HC(At disease onset (study baseline) and at week 10)
- Assessment of testosterone/cortisol ratio in EAD, IAD, PS patients and HC in accordance with BDNF rs6265 gene polymorphism and gender(At disease onset (study baseline) and at week 10)
- 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(At disease onset (study baseline) and week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of HAM-A scores in EAD, IAD,PS and HC(At disease onset (study baseline) and week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum BDNF (ng/ml) levels in EAD, IAD,PS and HC(At disease onset (study baseline) and at week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of serum testosterone (ng/dL) levels in EAD, IAD,PS and HC(At disease onset (study baseline) and at week 10)
- Unpaired, two-way ANOVA and Bonferroni means separation tests for multiple comparisons of testosterone/cortisol ratio in EAD, IAD, PS and HC(At disease onset (study baseline) and at week 10)
- Correlation analysis of studied parameters in dermatological patients and HC(At disease onset (study baseline) and week 10)
研究者
Tatyana Vinnik
Assistant Professor
Astana Medical University