Depression
Conditions
Brief summary
The study aims to evaluate or to assess: * An improvement in the peripheral inflammatory levels in depressed patients after 8 weeks of treatment with Minocycline in addition to their current antidepressant treatment; * Any improvements in depressive symptoms after 8 weeks of treatment with Minocycline given as adjuvant to the current antidepressant treatment; * Changes in the inflammatory status in the brain (in terms of microglia activation with 11C PK PET) after 8 weeks of treatment with Minocycline in addition to the current patient's treatment; * Possible structural and functional brain changes evaluated by MRI after 8 weeks of treatment with Minocycline given as adjuvant to the current patient's treatment; * Whether changes in MRI, in microglia activation, and peripheral inflammation correlate with the improvement in depressive symptoms. In order to achieve these, a total of 60 patients, male and female, aged 25-45, who have not responded to their pharmacological treatment and who have medium-high levels of inflammation (with CRP\> 2 mg/L) will be included in the study. Enrolled patients will receive, in addition to their current antidepressant treatment, Minocycline (200 mg/day as total dosage) for 8 weeks. Patients will be subjected to blood collection and clinical evaluations at baseline and after 8 weeks of treatment with Minocycline. A subgroup of patients will be subjected to MRI and 11C PK PET assessment at baseline and after 8 weeks of treatment with Minocycline.
Interventions
DRUGMinocycline
Minocycline (200 mg/day) for 8 weeks with a single daily administration (2 hard capsules of 100 mg)
Sponsors
Ospedale San Raffaele
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Being male or female depressed patients (aged 25-45); 2. Having a current DSM-V diagnosis of non-psychotic major depressive disorder confirmed by SCID; 3. Being non-responder to a current SSRI for at least 8 weeks, and historically to one other SSRI; 4. Being in stable antidepressant therapy for at least 8 weeks; 5. Being tolerant to the current SSRI; 6. Accepting Minocycline treatment; 7. Having CPR level\> 2 mg/L; 8. Having signed and dated an informed consent to participate in the study; 9. Having no contraindications to receive treatment with Minocycline; 10. Having no contraindications to undergo the 11C-PK PET scan.
Exclusion criteria
1. Having active suicidal ideation; 2. Having a primary diagnosis of bipolar disorder, obsessive-compulsive disorder, eating disorder, PTSD; 3. Having a history of substance/alcohol abuse; 4. Having received tetracycline therapy within the previous 2 months; 5. Having a history of sensitivity to this class of drugs; 6. Having acute infections or an autoimmune or inflammatory disorder; 7. Having CRP\>20 mg/L, as indicates acute infection or other major pathology; 8. Being sensitive to Minocycline; 9. Having a history of severe allergy or hypersensitivity to drugs; 10. Being hypersensitive to the active substance, to other tetracyclines or to any of the excipients; 11. Having severe renal failure; 12. Having hepatic dysfunction; 13. Being pregnant and in lactation; 14. (for MRI) Having pacemakers, electromechanical devices, ferromagnetic vascular clips, cochlear implants, stapedial prostheses, ferromagnetic foreign bodies, sickle cell anemia;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in the peripheral inflammatory status assessed by the measurement of CRP levels and inflammatory markers (i.e. IL-1, IL-6, IL-17 and TNF-alpha) | Changes from baseline to week 8 | To evaluate an improvement in the peripheral inflammatory status in depressed patients after 8 weeks of treatment with Minocycline in addition to their current pharmacological treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in depressive symptoms assessed by HAM-D17 | Changes from baseline to week 8 | To assess any improvements in depressive symptoms after 8 weeks of treatment with Minocycline given as adjuvant to the current antidepressant treatment. |
| Changes from baseline in central inflammatory levels by PET and by assessing differences in PK11195 binding | Changes from baseline to week 8 | To evaluate changes in the inflammatory status in the brain (in terms of microglia activation with 11C PK PET) after 8 weeks of treatment with Minocycline in addition to the current patient's treatment; |
| Structural and functional brain changes by MRI | Changes from baseline to week 8 | To evaluate by MRI possible structural and functional brain changes after 8 weeks of treatment with Minocycline given as adjuvant to the current patient's treatment. |
| Changes from baseline of the associations among brain structure observed with MRI, activation of microglia by PET, peripheral inflammatory markers and depression assessment scales | Changes from baseline to week 8 | Identification of correlations between a reduction of peripheral inflammation (by CRP and cytokines levels in blood samples) and/or central inflammatory status (by MRI and PET) and an improvement in depressive symptoms (evaluated by HAM-D17, SCID-5, BDI-II, STAI and CGI scale), after 8 weeks of treatment with Minocycline. Correlations will be calculated by using Pearson or Spearman correlation coefficients (statistical measures to analyse the relationship between variables with different units of measurement). |
Countries
Italy
Outcome results
None listed