TSPO ligands in the treatment of depression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Einrichtungen des Bezirks Oberpfalz KU AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

25 Jul 2024 → 21 Nov 2025

Decision date (initial)

2024-07-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

German Research Foundation (DFG)

External identifiers

EU CT number

2024-512698-29-00

EudraCT number

2021-006773-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Therapy

The primary goal of the study is to investigate the effects of add-on treatment with the TSPO ligand etifoxine in addition to TAU on clinical symptoms in patients suffering from unipolar/bipolar depressive disorder. Clinical symptoms will be assessed by the grade of depression using the Hamilton Scale for Depression (HAMD-21) several times up to day 15 of treatment.
Does add-on treatment with the TSPO ligand etifoxine for 14 days accelerate (reduction of ET50) the response compared to add-on treatment with placebo in addition to TAU?

Secondary objectives 8

1. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to an increased treatment response (increase of Emax parameter)?
2. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to a reduction of the HAM-D score on day 15?
3. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to altered synthesis of neurosteroids, TSPO Expression and/or acitivty of the HPA axis?
4. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to altered cognitive functions like memory or emotional processing assessed by a neuropsychological test battery?
5. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to changes of functional neuronal networks and cognitive functions assessed using functional magnetic resonance imaging (fMRI) by using resting-state measurements and task-based paradigms?
6. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to changes of microbiome composition?
7. Does add-on treatment with the TSPO ligand etifoxine in depressive patients compared to add-on treatment with placebo in addition to TAU lead to changes of odour capacity?
8. Does cessation of intake of the TSPO ligand lead to a relapse or withdrawal symptoms?

Conditions and MedDRA coding

Unipolar/bipolar depressive disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Inpatient treatment in the Bezirksklinikum Regensburg
2. Male and female patients in the age between 18 and 65 years
3. Voluntary admission to hospital independent from the trial
4. Diagnosis of unipolar (ICD-10: F32, F33) or bipolar depression (ICD-10: F31.3-5)
5. HAMD-21 score > 18
6. Ability to conceive nature, meaning and consequences of participation in the clinical trial and to understand and implement the explanations concerning the study as well as the instruction
7. Written informed consent after the trial has been comprehensively explained
8. Indication for pharmacological treatment independent of the trial
9. Willingness to forgo the consumption of alcohol during participation in the study
10. Willingness to forgo to drive a car or to operate heavy machines
11. Women of Childbearing Potential (WOCBP) need a negative pregnancy test (serum ß-hCG = serum human chorionic gonadotropin) at inclusion and have to be willing to use reliable contraception during the study (eg. oral contraceptives, hormone containing intrauterine coils, dermal or injectable contraceptives with longterm effects, tubal ligation). WOCBP are defined as women after menarche, which are not post-menopausal (at least 12 months no menstruation) und which did not undergo a documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy.
12. Patients with partners in a reproductive age must be willing to use appropriate contraceptives (Pearl-Index < 1%) for the duration of the study
13. During pregnancy of the partner the patients have to use a condome during sexual intercourse

Exclusion criteria 20

1. Diagnosis of a comorbid mental disorder like schizophrenia, addiction disorders according to ICD-10, or presence of another psychiatric main diagnosis in accordance with ICD-11 diagnosed using the M.I.N.I.
2. Diagnosis of an acute somatic or neurological disease
3. Acute suicidality
4. Contraindications of the IMP: myasthenia, state of shock, severely impaired liver and/or renal function
5. Contraindications against the implementation of functional Imaging (pacemaker, metal implants, tattoos in the head/neck area)
6. Permanent treatment with 5alpha-reductase-inhibitors, pregabaline or gabapentine over 2 weeks prior to participation in the study
7. Heart rate (HR) < 45 or > 110 bpm
8. Clinically relevant impairments in ECG
9. Blood pressure: systolic < 90 or > 165 mmHg, diastolic < 50 or > 95 mmHG
10. Body temperature < 35°C or > 37.5°C
11. BMI < 19 bzw. > 35
12. Abnormal laboratory parameters of clinical relevance before study inclusion: Excess of thresholds: GPT, GOT and γ-GT above 20 %, creatinine up to 0,2 mg/dL above age-adapted threshold; excess of the normal range more than twice as much of the upper standard or underrun of more than half of the lower standard for the other laboratory parameters (erythrocytes, leucocytes, thrombocytes, hemoglobin, hematocrit, MCH, MCHC, MCV, lymphocytes, monocytes, eosinophils, basophils, neutrophils, natrium, potassium, calcium, transferrin, ferritin, urea, uric acid, sober glucose, overall protein, triglycerides, cholesterol, HDL, LDL, C-reactive protein (CRP), bilirubin, TSH, free Trijodthyronin (fT3), free Thyroxin (fT4), Quick, PTT, HbA1c)
13. Pregnancy or nursing period
14. Abuse of alcohol or drugs within the last 12 months before the inclusion screening diagnosed using the M.I.N.I.
15. Dependence of alcohol or drugs in the medical history diagnosed using the M.I.N.I.
16. Known allergy or hypersensitivity against Etifoxine Hydrochloride or one of the other components (talc, docusate sodium, sodium benzoate, preagglutinated starch, microcrystalline cellulose, Lactose Monohydrate, Magnesium stearate (Ph. Eur.), highly-dispersed silicon dioxide, titanium dioxide, Indigotine, Erythrosin)
17. Galactose intolerance, lack of lactose, glucose-galactose malabsorption
18. Celiac disease, non-celiac-non-wheat allergic-wheat sensitivity (NCHS)
19. Positive drug screening (amphetamines, cannabis, opiates, cocaine, Ethylglucuronid, Ethanol, Fentanyl, Pregabalin, Buprenorphine, Methadone)
20. Concurrent participation in another clinical trial according to AMG

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ET50 estimated based on the HAMD-21 scores assessed at the baseline and days 1, 2, 3, 4, 5, 6, 7, 8, 15, 22 and 29 after start of the treatment

Secondary endpoints 19

1. HAMD-21 score at baseline and on days 1, 2, 3, 4, 5, 6, 7, 8, 15, 22 and 29 after start of the treatment
2. PHQ-9 score at baseline and on days 1, 2, 3, 4, 5, 6, 7, 8, 15, 22 and 29 after start of the treatment
3. VAS-scores at baseline and on days 1, 2, 3, 4, 5, 6, 7, 8, 15, 22 and 29 after start of the treatment
4. BDI-score at baseline and on days 8, 15, 22 and 29 after start of treatment
5. HAM-A score at baseline and on days 8, 15, 22 and 29 after start of treatment
6. MADRS score at baseline and on days 1, 2, 3, 4, 5, 6, 7, 8, 15, 22 and 29 after start of the treatment
7. SSS score at baseline and on days 8, 15, 22 and 29 after start of treatment
8. C-SSRs score at baseline and on days 8, 15, 22 and 29 after start of treatment
9. Adverse events on days 1, 8, 15, 22 and 29 after start of treatment
10. Neurosteroids in serum (pregnenolone, progesterone, 5α-dihydroprogesterone, allopregnanolone, epipregnanolone, pregnanolone, corticosterone, deoxycorticosterone) at baseline and on day 15 after start of treatment
11. TSPO expression in thrombocytes at baseline and on day 15 after start of treatment
12. Cortisol Awakening Response (CAR) at baseline and on day 15 after start of treatment measured in saliva directly as well as 30 and 60 minutes after awakening
13. Cognitive functions assessed with the CANTAB test battery at baseline and on day 15 after start of treatment
14. Amplitude changes of the blood oxygenation level in fMRI signal (BOLD) during a learning task at baseline and on day 15 and 29 after start of treatment
15. Representational dissimilarity of emotional stimuli at baseline and on day 15 and 29 after start of treatment
16. Functional connectivity and connectivity dynamics at baseline and on day 15 and 29 after start of treatment
17. Alpha diversity (number of species in one habitat) of the microbiome at baseline and on day 15 and 29 after start of treatment
18. Beta diversity (development of the number of species in one habitat) of the microbiome at baseline and on day 15 and 29 after start of treatment
19. Odour capacity quantified by the SDI-score at baseline and on day 15 and 29 after start of treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Einrichtungen des Bezirks Oberpfalz KU AöR

Sponsor organisation

Medizinische Einrichtungen des Bezirks Oberpfalz KU AöR

Address

Universitaetsstrasse 84, Kumpfmuehl-Ziegetsdorf-Neupruell Kumpfmuehl-Ziegetsdorf-Neupruell

City

Regensburg

Postcode

93053

Country

Germany

Scientific contact point

Organisation

Medizinische Einrichtungen des Bezirks Oberpfalz KU AöR

Contact name

Prof. Dr. med. Rainer Rupprecht

Public contact point

Organisation

Medizinische Einrichtungen des Bezirks Oberpfalz KU AöR

Contact name

Prof. Dr. med. Rainer Rupprecht

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications