BIPLONG - The Bipolar Disorder in the Longitudinal Course

Bipolar Disorder Clinical Trial

— BIPLONG  

Official title:

The Bipolar Disorder in the Longitudinal Course- Genom-wide Analysis of the genotype1 - phenotype2- Relationships in the Longitudinal Course of Psychosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05064995
• Other study ID #: 25-355 ex 12/13
• Status: Recruiting
• Start date: June 13, 2013
• Est. completion date: June 13, 2022

Study information

• Verified date: September 2021
• Source: Medical University of Graz
• Contact: Eva Reininghaus, MD, PhD, MBA
• Phone: +43 316 385 80968
• Email: eva.reininghaus[@]medunigraz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 560
• Est. completion date: June 13, 2022
• Est. primary completion date: June 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Bipolar Disorder

Locations

Country	Name	City	State
Austria	Medical University Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CVLT- california verbal learning test	The California Verbal Learning Test (CVLT) provides a brief and individualized assessment of verbal learning strategies and processes. The higher the score, the better the outcome	at six months
Primary	STROOP Farbe-Wort-Interferenz-Test (FWIT)	As an objective and reliable multidimensional performance test, the Color-Word. The Interference Test measures elementary information processing skills (selection, encoding, and decoding) in the visual-verbal functional domain. The lower the score, the better the outcome.	at six months
Primary	D2-R	To measure the subject's ability to concentrate and the speed and accuracy in distinguishing similar visual stimuli. The higher the score, the better the outcome.	at six months
Primary	"Reading the eyes of the mind" =Theory of mind	measurement of the ability to detect social cues. The higher the score, the better the outcome.	at six months
Primary	Trail Making Test A/B, TMT-A	Measurement of cognitive processing speed, as well as linguistic, executive, and attentional components. The lower the score, the better the outcome.	at six months
Primary	Mehrfachwahl Wortschatz Test (MWT-B)	Measurement of the general intelligence level. The higher the score, the better the outcome.	at six months
Primary	Number Symbol Test	Measurement of processing speed. The higher the score, the better the outcome.	at six months
Primary	Number Repeat	Measurement of working memory. The higher the score, the better the outcome.	at six months
Primary	Beck Depressions Inventar II (BDI-II)	Measurement of depression severity; 21 items on a scale of 0-3 (ascending). The higher the score, the worse the outcome.	at six months
Primary	Manie-Selbstbeurteilungsskala (MSS) (self-rating scale)	Measurement of manic symptoms; 48 items (dichotomous). The higher the score, the worse the outcome.	at six months
Primary	Questionnaire of religiosity	socio-demographic assesment of religiosity; 2 items.	at six months
Primary	Big Five Inventory-10 (BFI-10)	Measurement of personality variables; 10 items on a scale of 1-5 (ascending).	at six months
Primary	World Health Organisation Quality of Life (WHOQOL Bref)	Measurement of life-quality and health; 26 items on a scale of 1-5 (ascending).	at six months
Primary	Life Event Questionnaire (LEQ)	Measurement of life events and their influence; 79 items on a scale of 0-3 (ascending)	at six months
Primary	Temperament and affective disorders (TEMPS-A)-Scale	35 items on a scale of 1-5 (ascending). The higher the score, the better the outcome.	at six months
Primary	Brief symptom inventory (BSI)	Measurement of psychological symptoms; 53 items on a scale of 0-4 (ascending). The higher the score, the worse the outcome.	at six months
Primary	Anhedonia scale (AS)	Measurement of Anhedonia; 14 items on a scale of 1-4 (ascending). The higher the score, the worse the outcome.	at six months
Primary	Maslach Burnout Inventory (MBI-GS-D)	Measurement of burnout symptoms; 16 items on a scale of 1-6 (ascending). The higher the score, the worse the outcome.	at six months
Primary	Resources in Sexuality and Partnership (RSP)	Measurement of relationship emotions; 25 items on a scale of 1-5 (ascending).The higher the score, the better the outcome.	at six months
Primary	Satisfaction in the couple relationship (ZIP)	Measurement of relationship satisfaction; 7 items on a scale of 1-5 (ascending), 3 items open questioned. The higher the score, the better the outcome.	at six months
Primary	Demographic Data	Measurement of demographic data	at six months
Primary	Questionnaire of current life situation	Measurement of demographic and diagnostic data;	at six months
Primary	Anthropometric Data - weight	Measurement of weight	at six months
Primary	Anthropometric Data- height	Measurement of height	at six months
Primary	Anthropometric Data - waist-to-hip ratio	Measurement of waist-to-hip ratio	at six months
Primary	Anthropometric Data - blood pressure	Measurement of blood pressure	at six months
Primary	Clinical Global Impression (CGI)	External rating of a symptom severity; 2 items on a scale of 0-7 (ascending). The higher the score, the better the outcome.	at six months
Primary	Global Assessment Scale of Functioning (GAF)	External rating of level of functioning; 1 item on a scale of 1-100 (ascending). The higher the score, the better the outcome.	at six months
Primary	Hamilton Depression Scale (HAMD)	External rating of depression symptoms; 21 items on a scale of 0-4 (ascending).The higher the score, the worse the outcome.	at six months
Primary	Young Mania Rating Scale (YMRS)	External rating of manic symptoms; 11 items on a scale of 0-4/0-8 (ascending). The higher the score, the worse the outcome.	at six months
Primary	Specific Level of Functioning Assessment and Physical health Inventory (SLOF)	External rating of functioning; 43 items on a scale of 1-5 (ascending), 2 items open questioned. The higher the score, the better the outcome.	at six months
Primary	Supplementary Data for External Rating	External rating of bipolar symptoms; 7 items.	at six months