Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04423471 |
| Other study ID # |
PI-16-150 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2021 |
| Est. completion date |
December 2022 |
Study information
| Verified date |
January 2022 |
| Source |
Germans Trias i Pujol Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Objectives: To identify peripheral neuroinflammatory markers in patients suffering from major
depression or psoriasis in relation to affective symptoms (anxiety, depression,
irritability), fatigue and cognitive symptoms; and their change after specific treatments.
Methodology: Observational prospective cohort study in patients diagnosed with major
depression and patients with plaque psoriasis, who naturalistically undergo different
treatments (systemic or biological for psoriasis, antidepressants for depression). Forty-one
patients with major depression attending psychiatric consultations and 82 patients with
psoriasis attending dermatology consultations at Hospital Universitari Germans Trias i Pujol
aged 18 to 65 years old will be selected for inclusion. All of them will be assessed at
baseline and after 4 months treatment through a series of demographic and clinical variables,
psychiatric diagnosis, psychopathological scales and immunological and biochemical variables
after blood draw for obtaining serum, peripheral blood mononuclear cell (PBMC) and extraction
of total RNA. Investigators will analyze the correlation between immunological markers and
affective and cognitive symptoms at baseline, as well as their variation after treatment.
Subsequently, a bivariate comparative analysis will be carried out, where statistically
significant or marginally significant variables associated with psychopathological variables
will be used to construct a multivariate model of binary logistic regression.
Description:
Design This is a prospective observational study of cohorts with patients diagnosed with
major depression or psoriasis and subjected to different treatments with systemic or
biological drugs in the case of psoriasis, and with antidepressants in the case of major
depression.
Subjects of study The subjects that will participate in this study will be outpatients
treated in the Dermatology Consultations and the Psychiatric Consultations of the Germans
Trias i Pujol University Hospital (Badalona, Spain), clinically diagnosed with psoriasis or
major depression.
Inclusion criteria:
- Age between 18 and 65
- Clinical diagnosis of 1) In the psoriasis group: diagnosis of plaque psoriasis made by a
dermatologist, lasting at least 6 months; 2) In the major depression group: clinical
diagnosis of major depression according to DSM-5 criteria made by a psychiatrist.
- Patients receiving systemic or biological treatment for psoriasis, or antidepressant for
major depression.
Exclusion criteria:
- Previous treatments for psoriasis: narrow band ultraviolet B radiation (NBUBR)
phototherapy in the last 2 weeks; Psoralene+ultraviolet A (PUVA) phototherapy in the
last 4 weeks; conventional systemic treatments in the last 4 weeks; biological
treatments in the last 3 months
- Previous antidepressant treatments in the last 6 weeks
- Antipsychotic or eutimizing treatments in the last 6 weeks
- The presence of concurrent psychotic symptoms
- Alcohol or drug use disorders, with active consumption during the last 3 months
- Pregnant women
- Serious and / or unstable medical disorders, Addison or Cushing's disease, Rheumatoid
arthritis or systemic lupus erythematosus.
Patients will be assigned to three groups:
- Group 1 - psoriasis patients who will receive systemic treatment (mainly methotrexate)
- Group 2 - psoriasis patients who will receive a biological treatment
- Group 3 - patients with major depression who will receive an antidepressant treatment
Sample's size calculation The required sample size has been calculated based on the possible
differences in the biomarkers: C reactive protein (CRP), interleukin IL-6, etc. Accepting an
alpha risk of 0.05 and a beta risk of less than 0.2 in a bilateral contrast, 41 subjects are
needed in each of the three groups to detect a difference equal to or greater than 2/3 of the
standard deviation. A follow-up loss rate of 10% has been estimated. Therefore, a total of
123 patients will be evaluated.
Variables
- Sociodemographic variables: Sex / Age / Marital status / Level of studies completed /
Employment status
- General clinical variables
- Body mass index (BMI)
- Medical comorbidities and Charlson Comorbidity Index
- Active drug treatments
- Clinical psoriasis variables
- BSA (Body Surface Area). Calculation of the body surface covered by injuries.
- PASI (Psoriasis Area and Severity Index). It is a measure of the severity and
overall coverage of psoriasis. All calculations are combined in a single score in
the range of 0 (absence of lesions) to 72 (the most severe case of psoriasis).
Similarly, ScalpPASI (PASI applied to the scalp) and PPPASI (PASI applied to
palmoplantar regions) will be calculated.
- DLQI (Dermatology Life Quality Index). This instrument consists of 10 questions
covering six domains (symptoms and feelings, daily activities, leisure, work and
school, personal relationships and concern for the treatment of psoriasis)
- Time since the diagnosis of psoriasis
- Previous treatments for psoriasis
- Clinical depression variables
- Psychiatric diagnoses according to clinical interview and Diagnostic and
Statistical Manual of Mental Disorders (DSM-5) criteria (Structured Clinical
Interview for DSM-5 (SCID-5).
- Age of onset and time of evolution from the first episode of major depression
- Time of evolution of the current episode of major depression
- Previous treatments for depression
- Psychopathological variables
- HADS (Hospital Anxiety and Depression Scale)
- PHQ-9 (Patient Health Questionnaire)
- MADRS (Montgomery Asberg Depression Rating Scale)
- GAD-7 (Generalized Anxiety Disorder 7-item scale)
- SHAPS (Snaith-Hamilton Pleasure Scale)
- The Irritability Questionnaire
- PSS (Perceived Stress Scale)
- FSS (Fatigue Severity Scale)
- MoCA (The Montreal Cognitive Assessment)
- Immunological and biochemical variables:
- Acute phase biomarkers: C Reactive Protein (CRP)
- Proinflammatory cytokines: IL-1β, IL-6, TNF-α, IL-12, IL-23, IL-17
- Anti-inflammatory cytokines: IL-10, IL-4, Transforming growth factor-β (TGF-β)
- Hypothalamus-pituitary-adrenal axis (HPA): Cortisol
- Oxidative and nitrosative stress: Zinc, Glutathione, Albumin, Uric acid, Bilirubin
- Microglia activation: miR-155, miR-126, miR223, miR146a, miR-21, miR-124
- Neurogenesis: Brain-derived neurotrophic factor (BDNF) in serum
- Lymphocyte subpopulations in peripheral blood (Th1, Th2, Th17, Th1 / 17, Treg, ship
cells, central memory and effector memory)
- Result variables:
- Response to treatment (changes in PASI or MADRS scores)
Data collection and analysis All outpatients with the diagnosis of psoriasis attended in the
Dermatology Consultations of the Germans Trias i Pujol Hospital, as well as all those
patients with the diagnosis of major depression treated in the Psychiatric Consultations of
the same center, will be evaluated for the recruitment.
- Recruitment visit: It will be performed by one of the dermatologists (in the psoriasis
group) or by one of the psychiatrists (in the major depression group) participating in
the study. The patient will be informed about the study and their written consent will
be requested. Subsequently, the inclusion and exclusion criteria will be reviewed, and
all demographic and clinical variables will be collected.
- Baseline visit: A blood collection will be performed to collect serum and PBMC
(peripheral blood mononuclear cells). Serum samples will be centrifuged at 1750 rpm for
10 minutes, the supernatant will be collected and frozen at -20 ° C in the Immunology
Laboratory of the Germans Trias i Pujol Institute. For PBMC, Ficoll gradient
centrifugation of blood samples with anticoagulant will be carried out. Once the PBMCs
are separated, they will be frozen with 20% dimethyl sulfoxide (DMSO) in Roswell Park
Memorial Institute (RPMI) culture doctor with 20% fetal calf serum (FCS) and stored in
liquid nitrogen in the Cryobiology Platform of the Germans Trias i Pujol Institute.
Blood samples will also be obtained for the total extraction of RNA with 3 ml of
Paxgene® tubes, processed and frozen at -80 ° C in the immunology laboratory / Also in
this baseline visit, one of the psychiatrists will visit the patient and apply the
interview semi-structured clinic and psychopathological evaluation questionnaires.
- Follow-up visit after 16 weeks of treatment: Clinical variables will be collected and
the same procedures as during the baseline visit will be performed.
Statistical analysis First, a descriptive analysis of the sample will be carried out.
Categorical variables will be summarized with frequencies and percentages, while quantitative
variables will be described with the mean and standard deviation if they have a normal
distribution, or the median and the 25th and 75th percentiles otherwise.
Secondly, the correlation between the severity of psoriasis (PASI) at the baseline visit (in
all patients) and the different scores of the psychopathological scales will be analyzed.
Since the PASI does not follow a normal distribution, it will be carried out with the
Spearman linear correlation test (Spearman rho).
Subsequently, a bivariate comparative analysis between the analytical and psychopathological
variables will be carried out. Categorical variables will be compared with Fisher's square or
exact Chi test, according to the application conditions, and quantitative variables with the
Student's T test for independent data or the non-parametric Mann-Whitney U test. The
statistically significant or marginally significant variables (P <0.01) associated with
psychopathological variables in the bivariate analysis will be used to construct a
multivariate model of binary logistic regression, in order to evaluate the joint factors with
greater discrimination capacity of each of the psychopathological variables. For the model,
the odds ratio will be displayed along with its 95% confidence intervals and the model
calibration will be evaluated with the Hosmer and Lemeshow test and its ability to
discriminate using Receiver Operating Characteristic (ROC) curves. In all cases, P values
below 0.05 will be considered statistically significant. The analysis will be carried out
with the SPSS 22.0 software.
Limitations of the study The study is conducted in a tertiary referral hospital, so the
sample of patients with psoriasis or major depression may not be representative of the
general population of patients with these diseases.
Psychopathological measures are carried out through fully validated questionnaires in Spanish
in different population samples, including populations with comorbid medical conditions, but
not specifically in patients with psoriasis, except for DLQI.
Patients with psoriatic arthritis, although with high levels of inflammation, are likely to
be on chronic treatment with anti-inflammatory drugs that may affect the results. In any
case, the use of these treatments will be used as a covariate.
Ethical aspects The project will be submitted to the Ethical Research Committee (ERC)-Germans
Trias i Pujol University Hospital for approval. Subjects will be included once they have
given their informed consent. The ethical principles of the Declaration of Helsinki
(Fortaleza, 2013), the Standards of Good Clinical Practice, the legislation on biomedical
research (Law 14/2007), the obtaining and processing of biological samples and biobanks (RD
1716) will be respected. / 2011) and clinical trials with medications (RD 1090/2015). The
data will be processed in accordance with Organic Law 15/1999, on the Protection of Personal
Data.
