Neurobiological Analyses Within the FORESEE III Study

University Hospital Freiburg

Status: Unknown

Conditions: Treatment Resistant Depression

Study type: Observational

Funder types: Other

Identifiers

NCT04021823

40418

Details and patient eligibility

About

In this observational, non-invasive clinical study different neurobiological analyses will be performed in a group of patients with severe treatment resistant major depression participating in an efficacy study of deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB) - FORESEE III.

Full description

This study is a sub-project of the FORESEE III study (Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression). The FORESEE III study itself is a randomized, sham-controlled, double blind (patient and observer blinded) clinical trial to assess the antidepressant effect of DBS compared to sham.

The aim of this sub-project is to analyze the time-course of biological correlates of treatment resistant major depression as well as neurobiological markers of treatment response to treatment with DBS in a well-characterized patient population during 12 month of DBS.

Specific neurobiological analyses include testing of

1. epigenetic markers (DNA methylation in candidate genes of depression and epigenome-wide association studies, EWAS)
2. markers of neuroinflammation (cytokines, neuropeptides and other immune factors)
3. micro RNAs and transcriptome signatures
4. markers of neurodegeneration (neurofilament light protein)
5. metabolomic analyses and
6. endocrinological parameters including glucose tolerance.

All markers will be tested in blood samples (and urine samples for metaboloic profiling) before neurosurgery as well as at several time points during DBS and sham condition intervals.

Additionally hemodynamic parameters will be analysed at test stimulation of the slMFB during neurosurgery.

The results will be correlated with clinical and other biological response parameters of the FORESEE III study and are hypothesized to indicate treatment response as well as allowing prediction of response to DBS. All neurobiological analyses will be linked in a tightly integrated and comprehensive translational approach.

Further, a volunteer group of healthy controls will be recruited and tested for blood-markers of neurodegeneration (neurofilament light protein, 4.) as well as metabolomic analyses in blood and urine (5.).

Enrollment: 50 estimated patients

Sex: All

Ages: 20 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

DBS Patients:

Inclusion Criteria:

• All enrolled subjects of the Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression (FORESEE III) may participate in this study.

Exclusion Criteria:

• Non-Caucasian (because of requirements for genetic/epigenetic analyses)
• Somatic diseases like diabetes, cancer and severe liver- and kidney-diseases

Healthy Controls:

Inclusion Criteria:

• All healthy volunteers without any clinically significant psychiatric or somatic symptoms are eligible.

Exclusion Criteria:

• Any clinically significant psychiatric symptoms
• Conditions like diabetes, cancer or severe liver- and kidney diseases
• Drug or alcohol abuse

Trial design

50 participants in 2 patient groups

DBS patients

Description:

Patients with treatment resistant major depression participating in the FORESEE III study.

Healthy controls

Description:

Age- and sex-matched healthy controls undergoing analyses of neurodegenerative markers (neurofilament light protein) in blood and metabolomic analyses in blood and urine.