Simvastatin add-on Treatment to Standard Antidepressant Therapy in Patients With Comorbid Obesity and Major Depression

NCT04301271 | Completed Phase 2 DMC

• 1 other identifier: SIMCODE
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 9

Brief Summary

Major depressive disorder (MDD) and obesity are major contributors to impaired health worldwide. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomized controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Therefore, we hypothesize that Simvastatin add-on to standard antidepressant Escitalopram will improve depression to a greater extent than add-on placebo in patients with comorbid obesity and major depression. We will randomize 160 obese MDD patients at 8 recruiting centers to either Simvastatin or placebo as add-on to Escitalopram for 12 weeks. If successful, our trial would have immediate impact on clinical practice given the fact that Simvastatin and Escitalopram are available as inexpensive generic drugs with established safety.

Conditions

Depressive Disorder, Major; Obesity

Outcome Measures

Primary Outcomes (1)

• Change score in MADRS (Montgomery-Asberg-Depression Rating Scale)

  The MADRS is a rating scale to measure depression severity. Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where higher MADRS scores indicate higher levels of depressive symptoms.

  12 weeks

Secondary Outcomes (10)

• MADRS-response

  12 weeks

• MADRS-remission

  12 weeks

• MADRS-MCID

  12 weeks

• Change score in BDI-II (Beck Depression Inventory-II)

  12 weeks

• BDI-II-MCID

  12 weeks

Study Arms (2)

Simvastatin

EXPERIMENTAL

Simvastatin and Escitalopram

Drug: Simvastatin 40mg

Placebo

PLACEBO COMPARATOR

Placebo and Escitalopram

Drug: Placebo oral tablet

Interventions

Simvastatin 40mg DRUG

12 weeks 40 mg Simvastatin add-on

Also known as: Zocor, C10AA01

Simvastatin

Placebo oral tablet DRUG

12 weeks Placebo add-on

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, irreversible MAO inhibitor (e.g. tranylcypromine), 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

You may not qualify if:

• 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, Nevirapine, Etravirine).
• The patient uses Fibrates, Amiodarone, Amlodipine, Verapamil, Fluconazol, Diltiazem, Fusidic acid, Niacin or Lomitapide or BCRP-Inhibitors (e.g. Elbasvir or Grazoprevir)
• The patient uses Gemfibrozil, Ciclosporin or Danazol
• The patient has known hypersensitivity to other ingredients of Simvastatin and Escitalopram \[butylated hydroxyanisole, microcrystalline celluose, citric acid, starch, lactose, magnesium stearate, hypromellose, talc, titanium dioxide, iron oxides, colloidal silicon dioxide, croscarmellose sodium, polyethylene glycol\]
• The patient uses medication that is associated with QTc-prolongation \[antiarrhythmics class IA and III, antipsychotics (e.g. Haloperidol), phenothiazines, tricyclic antidepressants, antibiotics (e.g. Moxifloxacin), and certain antihistaminergic drugs (e.g. Astemizol, Mizolastine)\]
• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• NeuroCure Clinical Research Center, Charite, Berlin: collaborator
• University Medical Center Goettingen: collaborator

Study Sites (9)

Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie

Berlin, 12203, Germany

Location

Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Psychosomatik

Berlin, 12203, Germany

Location

Universitätsklinikum Frankfurt, Klinik für Psychiatrie, Psychosomatik und Psychotherapie

Frankfurt, 60528, Germany

Location

Universitätsmedizin Greifswald, Klinik und Poliklinik für Psychiatrie und Psychotherapie

Greifswald, 17475, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie

Hanover, 30625, Germany

Location

Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie

Leipzig, 04103, Germany

Location

Universitätsklinikum Schleswig-Holstein, Zentrum für Integrative Psychiatrie - Klinik für Psychiatrie und Psychotherapie

Lübeck, 23538, Germany

Location

Helios Hanseklinikum Stralsund Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik

Stralsund, Germany

Location

Related Publications (2)

• Otte C, Chae WR, Dogan DY, Piber D, Roepke S, Cho AB, Trumm S, Kaczmarczyk M, Brasanac J, Wingenfeld K, Koglin S, Wieditz J, Junghanns K, Lucht M, Prvulovic D, Kruger THC, Terock J, Haaf M, Hofmann T, Mauche N, Klein JP, Grabe HJ, Reif A, Kahl KG, Janowitz D, Leicht G, Hinkelmann K, Strauss M, Friede T, Gold SM. Simvastatin as Add-On Treatment to Escitalopram in Patients With Major Depression and Obesity: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Aug 1;82(8):759-767. doi: 10.1001/jamapsychiatry.2025.0801.

  PMID: 40465256 DERIVED

• Otte C, Chae WR, Nowacki J, Kaczmarczyk M, Piber D, Roepke S, Marschenz S, Lischewski S, Schmidt S, Ettrich B, Grabe HJ, Hegerl U, Hinkelmann K, Hofmann T, Janowitz D, Junghanns K, Kahl KG, Klein JP, Krueger THC, Leicht G, Prvulovic D, Reif A, Schoettle D, Strauss M, Westermair A, Friede T, Gold SM. Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial. BMJ Open. 2020 Dec 1;10(12):e040119. doi: 10.1136/bmjopen-2020-040119.

  PMID: 33262189 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Obesity

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Christian Otte, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: August 13, 2020
• Primary Completion: June 6, 2024
• Study Completion: June 6, 2024
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)