E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057840 |
E.1.2 | Term | Major depression |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary aim is to investigate association between changes in inflammatory biomarkers and improvement in depressive symptoms following adjunctive treatment with minocycline in treatment resistant depressed patients selected for increased inflammation. |
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E.2.2 | Secondary objectives of the trial |
The secondary aim is to identify molecular inflammatory pathways involved in the response to anti-inflammatory treatment in the same patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be aged 25-60 2. Have a current DSM-IV diagnosis of nonpsychotic major depressive disorder, confirmed by the Mini International Neuropsychiatric Interview (MINI); 3. Be non-responders to the current antidepressant taken at therapeutic doses for at least 6 weeks, as indicated by a current score of at least 14 on the 17-item Hamilton Depression Rating Scale (HAMD); 4. Be tolerant to the current antidepressant, and accepting augmentation with minocycline; 5. Have CRP levels ≥ 1 mg/L, indicative of mild-moderate inflammation; 6. Have the ability to understand and sign a written informed consent form prior to participation in any screening procedures and a willingness to comply with all trial requirements.
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E.4 | Principal exclusion criteria |
1. have active suicidal ideation of significant concern to require intensive monitoring by secondary psychiatry services; 2. have a primary diagnosis of bipolar disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or substance/alcohol misuse disorder; 3. are taking warfarin; 4. have received tetracycline within the previous 2 months, or have a history of sensitivity or intolerance to this class of drugs; 5. have an acute infection; or have an autoimmune or inflammatory disorder, because of both the rare but described association between minocycline and systemic lupus erythematosus, and the potential confounder effects of these conditions on immune biomarkers. 6. have hepatic or renal failure 7. take any other psychotropic medications other than their current antidepressant that has not been approved by a study investigator prior to enrolment 8. Refuse that we contact their General Practitioner (GP) to inform them about their participation in the study. 9. (Females) Have a positive pregnancy test before starting the study/are unwilling to take a pregnancy test and are unwilling to agree to use an acceptable form of contraceptive throughout the study period (e.g. condoms, IUD/IUS, injection, patch, ring). Female participants who use combined oral contraceptives as their main form of birth control will need to use an additional barrier method for the duration of treatment and for 7 days following completion of treatment. 10. Breastfeeding (females) 11. Are currently participating in a clinical trial of an investigational medical product (CTIMP). For individuals who have been recently on CTIMP clinical trials, we will decide on case by case basis if they could be included in the trial according to the type of trial they have been involved in.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes from baseline to Week 4 for Hamilton Depression Rating Scale total score, including the percentage of patients who show response, defined as 50% reduction in the baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Changes in depression scores will be evaluated at the end of the 4 weeks of treatment with either minocycline or placebo. |
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E.5.2 | Secondary end point(s) |
Clinical outcome: Changes from baseline to week 4 for Beck Depression Inventory, State and Trait Anxiety Inventory and Clinical Global Impression scale.
Biological outcome: Changes from baseline to Week 4 in cytokines and kynurenine pathway metabolites and transcriptomics.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The changes in clinical symptoms and biological measurements will be evaluated at the end of the 4 weeks of treatment with either minocycline or placebo. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will end when all patients have had their final visits, and all data is entered into the database, and all queries resolved and the database is locked. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |