Patients with comorbid obesity (body mass index = 30) and major depression
Conditions
Interventions
Trade Name: SimvaHEXAL®
Product Name: SimvaHEXAL®
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SIMVASTATIN
CAS Number: 79902-63-9
Concentration unit: mg milligram(s)
Concentration type: equ
Sponsors
Charité – Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent is present - The patient has the capacity to give consent (He/she is able to understand the nature and anticipated effects/side effects of the proposed medical intervention) - The patient has a major depressive episode according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders 5th Edition) - The patient has a score of = 18 in the Montgomery-Asberg Depression Rating Scale (MADRS) - The patient has a body mass index = 30 - The patient’s age is between 18 and 65 years (= 18 und = 65) - The patient has not given childbirth within the 6 months prior to study entry and is not breastfeeding - In case of non-psychotropic medication: The patient received stable pharmacological medication for at least 14 days prior to study entry (any changes in medication dose or frequency of therapy must be answered with no) - The patient did not take antidepressants during the last 7 days prior to study entry (discontinuation of effective medication to enable study participation is prohibited) - The patient did not receive prior treatment with Escitalopram in index episode - The patient had less than three ( 3 x upper limit normal (ULN)] and does not have elevated Carbohydrate Deficient Transferrin (CDT) = 2.4 % - The patient does not meet the criteria for alcohol use disorder (DSM-5: 303.90; ICD-10: F10.20) or substance use disorder (DSM-5: 304; ICD-10: F11.20 – F19.20) in M.I.N.I. for DSM-5 and a urine/serum drug screening is negative (except for benzodiazepines and opiates) - The patient does not have a history of suicide attempt - The patient does not have diagnosed epilepsy or increased bleeding diathesis or a history of angle closure glaucoma or other glaucomas - The patient did not have bariatric surgery prior to study entry - The patient does not have a known allergy or contraindication against Escitalopram or Simvastatin - The patient does not meet any of the following criteria: - hereditary muscle disease - known history of rhabdomyolysis - elevated creatine kinase (CK) outside of the sex-specific reference intervals - History of muscular symptoms under treatment with statins or fibrates - The patient does not have elevated TSH level outside of the age- and sex-specific reference intervals. - The patient does not have insulin-dependent diabetes mellitus - The patient does not have uncontrolled hepatic disorder, renal or cardiovascular disease - The patient does not have untreated hypothyroidism - The patient does not have a history of myocardial infarction or stroke - The patient does not have symptomatic peripheral arterial disease - The patient does not have monogenic familial hypercholesterolemia - The patient does not have clinically significant laboratory abnormalities - The patient did not participate in other interventional trials during the
Exclusion criteria
Exclusion criteria: - The patient has current use of statins (for visits 2-6 applies: except for IMP Simvastatin) - The patient has current use of antidepressants (for visits 2-6 applies: except for standard medication Escitalopram) - The patient has acute suicidal tendencies (MADRS Item 10 > 4) - The patient uses potent CYP3A4-inhibitors (e.g. clarithromycin, erythromycin, HIV protease inhibitors – see “Risks, adverse drug reactions, drug interactions, restrictions, contraindications, procedures in case of emergency”) - The patient uses potent CYP3A4 inductors (carbamazepine, efavirenz, nevirapin, etravirine). - The patient uses Fibrates, Amiodaron, Amlodipin, Verapamil, Fluconazol, Diltiazem, Fusidic acid, Niacin, Daptomycin or Lomitapid or BCRP-Inhibtors (e.g. Elbasvir or Grazoprevir) - The patient uses Gemfibrozil, Ciclosporin or Danazol - The patient has known hypersensitivity to other ingredients of Simvastatin and Escitalopram [butylated hydroxyanisole, microcrystalline celluose, citric acid, starch, lactose, magnesium stearate, hypromellose, talc, titanium dioxide, iron oxies, colloidal silicon dioxide, croscarmellose sodium, polyethylene glycol] - The patient uses medication that is associated with QTc-prolongation [antiarrhythmica class IA and III, antipsychotics (e.g. haloperidol), phenothiazines, tricyclic antidepressants, antibiotics (e.g. moxifloxacin), and certain antihistaminergic drugs (e.g. astemizol, mizolastin)] - The patient has clinically significant abnormalities in 12-lead ECG (e.g. QTc-prolongation = 500 ms or increase = 60 ms from baseline visit) - The patient is pregnant - The patient with childbearing potential is not willing to use an acceptable form of contraception (defined as Pearl index < 1) - The patient has current use of psychotropic medication (e.g. antipsychotics, anticonvulsants, lithium or St. John's Wort) except for benzodiazepines, non-benzodiazepines and opiates - The patient uses nonselective, irreversible monoamine oxidase (MAO) inhibitor (e.g. Tranylcypromine) or selective, reversible inhibitor of monoamine oxidase A (e.g. Moclobemide) or the nonselective, reversible monoamine oxidase inhibitor Linezolid - The patient is unwilling to consent to saving, processing and propagation of pseudonymized medical data for study reasons - The patient is legally detained in an official institution - The patient has active SARS-CoV-2 infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine whether add-on 40 mg/d Simvastatin to standard antidepressant medication (Escitalopram 20 mg/d) improves depression to a greater extent than adjunct placebo in patients with major depression and comorbid obesity;Secondary Objective: To examine whether add-on 40 mg/d Simvastatin to standard antidepressant medication (Escitalopram 20 mg/d) improves response rates, remission rates, patients’ impression of change, clinicians impression of severity and change, quality of life, social functioning, self-report depression, lipid values, and immunometabolism / mitochondrial function to a greater extent than adjunct placebo in patients with major depression and comorbid obesity;Primary end point(s): Change score from baseline to week 12 in Montgomery-Asberg-Depression Rating Scale (MADRS);Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints 1) MADRS-response (50 % MADRS score reduction from baseline), MADRS-remission (MADRS score < 10), and MADRS-minimal clinically important difference (MCID) 2) change Beck Depression Inventory (BDI-II) scores from baseline to week 12, and BDI-II-MCID Other secondary endpoints 2) change in Patients’ Global Impression of Change Scale (PGIC), change in Clinicians’ Global Impression of Severity of illness (CGI-S), Clinicians’ Global Impression of Improvement (CGI-I), EuroQol-5 Dimensions-3 Levels Questionnaire (EQ-5D-3L), and Social and Occupational Functioning Assessment Scale (SOFAS) from baseline to week 12 3) change in high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol from baseline to week 12 4) change in mitochondrial and cellular function of immune cells from baseline to week 12;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Countries
Germany
Contacts
Public ContactKlinik für Psychiatrie und Psychoth
Charité – Universitätsmedizin Berlin
Outcome results
None listed