Simvastatin add-on to Escitalopram in patients with obesity and depressio
- Conditions
- Patients with comorbid obesity (body mass index = 30) and major depressionTherapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2018-002947-27-DE
- Lead Sponsor
- Charité – Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
- 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) trials with antidepressants in index episode
- The patient does not have a history of non-response to Escitalopram
- The patient did not receive treatment with ketamine, electroconvulsive therapy (ECT) or other stimulatory treatments in index episode
- The patient does not meet any of the following criteria:
- schizophrenia
- schizoaffective disorder
- bipolar disorder
- The patient is not diagnosed with dementia and does not have moderate or severe impairment of general cognitive function according to clinical impression
- The patient does not have clinically relevant elevated liver enzymes [GOT or GPT > 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
- 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Secondary end point(s): Secondary efficacy endpoints<br>1) MADRS-response (50 % MADRS score reduction from baseline), MADRS-remission (MADRS score < 10), and MADRS-minimal clinically important difference (MCID)<br>2) change Beck Depression Inventory (BDI-II) scores from baseline to week 12, and BDI-II-MCID<br><br>Other secondary endpoints<br>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<br>3) change in high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol from baseline to week 12<br>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