Major depressive disorder
Conditions
Interventions
Trade Name: RoActemra
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Tocilizumab
CAS Number: 375823-41-9
Sponsors
Linköping University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General inclusions (evaluated through screening under separate protocol 2017/345-32) 1. Age 18 – 65 2. Working knowledge of Swedish 3. Current MDD episode as determined by MINI screening Tocilizumab augmentation-protocol related inclusions 1. Willingness to provide informed consent (including consent to use baseline data from protocol 2017/345-32), and ability to do so, as evidenced by clinical assessment and a MMSE score = 24 2. Serum IL-6 levels above upper limit of reference interval (evaluated under separate protocol 2017/345-32) 3. Women of childbearing potential (WOCBP) must agree to use a method of contraception that is highly effective for the duration of the study and for 3 months after the intake of the investigational medicinal product. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 61 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: General exclusions (evaluated under separate protocol 2017/345-32): 1. Any medical condition that, in the judgment of the study physician, after appropriate consults if needed, accounts for the symptoms of depression, such as, for example, hypothyroidism, severe anemia, etc. 2. Standard clinical contraindication to MRI scanning of the head according to MRI checklist in Region Östergötland, following additional exams and evaluation by radiologist if needed. 3. Pregnancy 4. Any medical condition that, in the judgment of the study physician and after appropriate consults if needed, is likely to influence cerebral blood flow or gross-level brain activity/anatomy, such as for instance: a. type-1 diabetes b. cardiovascular or respiratory disease c. history of significant head injury d. hyper-/hypothyroidism e. epilepsy 5. Current DSM-5 diagnosis of a substance use disorder (moderate – severe, corresponding to DSM-IV substance dependence; not including nicotine), as determined by the MINI interview 6. Current DSM-5 diagnosis of a psychotic disorder (except MDD episode with mood congruent psychotic symptoms) 7. Use of prescription or over-the-counter drugs that could interfere with the objectives of the study (such as ongoing use of steroidal and non-steroidal anti-inflammatory drugs) 8. Additional medication exclusions: a. For antidepressants i. new medications started within one month prior to study (two months, in the case of fluoxetine) ii. increase in dose within one month prior to study b. For antipsychotics i. changed dosage within one month prior to study c. For antiepileptic drugs i. changed dosage within two months prior to study d. For mood stabilizers (e.g., lithium) i. changed dosage within two months prior to study Tocilizumab augmentation-protocol related exclusions: 1. Presence, as evaluated by laboratory testing and appropriate specialist consult if needed, of multiple sclerosis, inflammatory bowel disease, or human immunodeficiency virus. 2. Recent (within past month) immunization or plan to receive immunization during the duration of the study. 3. Lactation 4. A history of, or current tuberculosis as determined by history, physical exam, blood tests and chest X-rays. 5. A history of, or current severe herpes infection (severe genital herpes, herpes zoster, or herpes encephalitis). 6. Having a high risk of tuberculosis exposure as confirmed by interview 7. Presence of interstitial pulmonary disease (including but not limited to primary or secondary pulmonary fibrosis or sarcoidosis), as determined by history, physical exam and chest X-ray. 8. Presence of hepatitis B or C as determined by laboratory testing 9. Systemic or serious fungal infection 10. A history of clinically significant recurrence of viral or bacterial infections, as determined from medical records and interview will lead to appropriate specialist consult to determine wheth
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the effects of administering tocilizumab on CNS-level biomarkers of inflammation in Major depressive disorder; Secondary Objective: To examine the effects of administering tocilizumab on depressive symptomatology As an exploratory objective: To explore whether the depressive and proinflammatory processes examined in the protocol are in any systematic way related to metabolic state, as indexed by visceral fat measured using a novel MRI procedure. ; Primary end point(s): The co-primary outcome measures will be change from baseline in central nervous system biomarkers of inflammation, as measured by 1) the free-water fraction on the post-augmentation MR-scan; and 2) levels of CSF pro-inflammatory cytokines. ; Timepoint(s) of evaluation of this end point: 1) the free-water fraction on the post-augmentation MR-scan: at Visit 6, i.e one week after last administration of IMP 2) levels of CSF pro-inflammatory cytokines: at Visit 7, i.e the last visit of the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcome will be change from baseline in levels of depressive symptomatology over time, as measured by the MADRS ratings acquired at Visits 2-6.;Timepoint(s) of evaluation of this end point: measured by the MADRS ratings acquired at Visits 2-6 (i.e once a week during 5 weeks, starting the same day as first injection of IMP and ends one week after last injection of IMP) | — |
Countries
Sweden
Contacts
Public ContactLinköping University
Linköping University
Outcome results
None listed