Clinical trial NCT05064995: BIPLONG - The Bipolar Disorder in the Longitudinal Course
Official title: The Bipolar Disorder in the Longitudinal Course- Genom-wide Analysis of the genotype1 - phenotype2- Relationships in the Longitudinal Course of Psychosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bipolar Disorder
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2021-10-01
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with bipolar disorder and healthy controls within the age frame of 18-75 are included.

Brief summary: The BIPLONG (The Bipolar Disorder in the Longitudinal Course ) study is a longitudinal study on the course of bipolar disorders and comprises two sub-studies: On the one hand, BIPLONG examines the genetic foundation and change in bipolar disorder, on the other hand, metabolic changes, clinical symptoms and cognition in bipolar disorders is evaluated. A current subproject of BIPLONG is the analysis of the psychological response of the COVID-19 (Corona virus disease) pandemic. With the parameters examined in BIPLONG, it is hoped to gain better understanding of the bipolar disorder in the longitudinal course.

Detailed description: Study Procedure:

In addition to the bipolar patients, healthy controls will also be included. The same inventories will be used for the control subjects and the same examinations or visits will be performed; bipolar-specific disease questions will not be asked in controls.

Intervention: Longitudinal study

Method:

All patients and controls undergo several assessments every six months:

Blood samples are collected with the following main parameters of interest being examined:

* Collection and analysis of DNA, establishment of permanent cell lines, determination of mRNA and gene products (proteins), proteomics, lipidomics.
* Routine parameters: Blood count, TSH, T3, T4, homocysteine, creatinine, amylase, lipase, CK, urea, uric acid, coagulation, HBA1c, glucose, lipids (triglyceryl, LDL, HDL, cholesterol, mass spectrometry), transaminases, CRP- levels, vitamin D.
* Biomarkers: oxidative stress parameters and antioxidants, neuroinflammatory markers (e.g. interleukins, tumor necrosis factor, interferons, GDNF, VEGF, etc.), neurotrophins (BDNF, NT, Trk..), insulin, IGF, adipokines, Apo-E and AAT analysis, tryptophan/kynurenine metabolites
* Intestinal hormones grehlin, glucagon-like peptides 1 and 2 (GLP-1/2) and cholecystokinin

Additionally, socio-demographic data and psychological data are collected by administering self-assessment questionnaires. Further, neurocognitive tests are administered.

The current psychological and psychiatric state of all subjects is examined by external ratings done by experts.

Anthropomethric measures are examined (waist-to-hip ratio, blood pressure, weight, height).

Additionally, MRI is conducted on all subjects (for patients every 6 months, for controls every 12 months).

Primary hypothesis:

* Gene-environment interactions are significantly contributory to bipolar affective disorder.
* There are pathologically altered neurobiological markers that play a role in the pathogenesis of bipolar disorder.
* There is an influence of anthropometric data on the course of bipolar disorder.

Statistical analysis and anticipated sample size:

Baseline data analysis will be investigated using a multi-factorial between subject design, with the variables of group (bipolar patients versus healthy controls), gender (males versus females), weight (normal weight versus overweight), etc. as independent factors, depending on the research question. As dependent variables, in addition to sociodemographic and clinical variables (number of episodes, etc.), physiological parameters (blood parameters, anthropometry and lipometer data, EEG, ECG, MRI) and psychological variables (psychological questionnaires) will be investigated. Likewise, covariates such as age or body mass index will be included as needed.

Correlation analyses (bivariate, partial) should show possible correlations between the variables. Discriminant analyses should find out which variable best separates the investigated groups (e.g. patients vs. controls). Furthermore, regression analyses (linear, multiple) will be performed to obtain additional information about the predictive value of the variables under investigation. All analyses will be computed using IBM SPSS Statistics 20.

For the "a priori analysis" of the follow-up study (T1-T5), a repeated measures design (repeated measures within factors) was adopted. The case number calculation (effect size d between .30 and .80; Cohen, 1988) for the F-test thus results in a sample size of 47 patients with a target effect size of .40 (power 95%; alpha .05; calculated with GPower 3.1). The correlation analyses at the first measurement time point (power .95, alpha .05, effect size: .35) yields 79 subjects per group (Pat. vs. controls) at all time-points.

Eligibility criteria: Inclusion criteria:

* Pat. with bipolar disorder, with an age between 18 and 85 years.
* Euthymic/ maximum mildly depressed at the time of consent (for this, the severity of depression will be determined using the Hamilton Depression Scale, this will also be included in any calculations).

Exclusion criteria:

* Pat. refuses participation
* Currently severely depressed/manic episode at the time of consent
* Other currently active severe mental/ brain organic disease (epilepsy, brain tumor..)
* St.p. severe craniocerebral trauma/ brain surgery.
* Reduced intelligence (IQ\< 70)
* Moderate/ severe dementia (Mini Mental Status Examination, MMSE, 20 and above)
* Clearly substance-induced clinical picture

Inclusion criteria healthy controls:

* For the whole procedure, made controls (age, gender) are needed. For this purpose we recruit controls by word of mouth or ask relatives of bipolar patients if they would like to participate. Patients are tested for the presence of a possible mental illness using Mini-DIPS (Diagnostisches Interview bei psychischen Störungen)
* Inclusion criteria: 18-75 years, no severe mental illness (depression, mania, psychosis; severe anxiety or obsessive-compulsive disorder requiring treatment, addictive disorder other than nicotine).

Exclusion criteria:

* First-degree relatives with severe mental illness.
* Severe active drug dependence (i.e. alcohol, benzodiazepines morphines)
* Current major depressive/ manic episode
* Other currently active severe mental/ brain illness (epilepsy, brain tumor..)
* St.p. severe craniocerebral trauma/ brain surgery.
* Congenital/ early childhood acquired intelligence impairment
* Moderate/ severe dementia (from MMSE 20)

Primary outcomes:
measure: CVLT- california verbal learning test
timeFrame: at six months
measure: STROOP Farbe-Wort-Interferenz-Test (FWIT)
timeFrame: at six months
measure: D2-R
timeFrame: at six months
measure: "Reading the eyes of the mind" =Theory of mind
timeFrame: at six months
measure: Trail Making Test A/B, TMT-A
timeFrame: at six months
measure: Mehrfachwahl Wortschatz Test (MWT-B)
timeFrame: at six months
measure: Number Symbol Test
timeFrame: at six months
measure: Number Repeat
timeFrame: at six months
measure: Beck Depressions Inventar II (BDI-II)
timeFrame: at six months
measure: Manie-Selbstbeurteilungsskala (MSS) (self-rating scale)
timeFrame: at six months
measure: Questionnaire of religiosity
timeFrame: at six months
measure: Big Five Inventory-10 (BFI-10)
timeFrame: at six months
measure: World Health Organisation Quality of Life (WHOQOL Bref)
timeFrame: at six months
measure: Life Event Questionnaire (LEQ)
timeFrame: at six months
measure: Temperament and affective disorders (TEMPS-A)-Scale
timeFrame: at six months
measure: Brief symptom inventory (BSI)
timeFrame: at six months
measure: Anhedonia scale (AS)
timeFrame: at six months
measure: Maslach Burnout Inventory (MBI-GS-D)
timeFrame: at six months
measure: Resources in Sexuality and Partnership (RSP)
timeFrame: at six months
measure: Satisfaction in the couple relationship (ZIP)
timeFrame: at six months
measure: Demographic Data
timeFrame: at six months
measure: Questionnaire of current life situation
timeFrame: at six months
measure: Anthropometric Data - weight
timeFrame: at six months
measure: Anthropometric Data- height
timeFrame: at six months
measure: Anthropometric Data - waist-to-hip ratio
timeFrame: at six months
measure: Anthropometric Data - blood pressure
timeFrame: at six months
measure: Clinical Global Impression (CGI)
timeFrame: at six months
measure: Global Assessment Scale of Functioning (GAF)
timeFrame: at six months
measure: Hamilton Depression Scale (HAMD)
timeFrame: at six months
measure: Young Mania Rating Scale (YMRS)
timeFrame: at six months
measure: Specific Level of Functioning Assessment and Physical health Inventory (SLOF)
timeFrame: at six months
measure: Supplementary Data for External Rating
timeFrame: at six months
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University Graz
state: Styria
Study officials:
References: