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Depressive Disorder, MajorPhase 2SIMCODENCT04301271

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

A Phase 2 study testing Simvastatin 40mg in people with Depressive Disorder, Major and Obesity, run by Charite University, Berlin, Germany at 9 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Depressive Disorder, Major, Obesity
What is being tested?
Simvastatin 40mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
161 participants
Where
9 sitesGermany
Study dates
13 Aug 2020to 6 Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • 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 refer-ence 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 6 months before and at the time of this trial
  • The patient is not an employee of the investigator study site, or a family member of the employees or the investigator, or otherwise dependent on the sponsor, the investigator or the investigator study site

Who cannot join

  • 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)
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  • 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
  • The patient is legally detained in an official institution

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie

    Berlin, 12203

  • Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Psychosomatik

    Berlin, 12203

  • Universitätsklinikum Frankfurt, Klinik für Psychiatrie, Psychosomatik und Psychotherapie

    Frankfurt, 60528

  • Universitätsmedizin Greifswald, Klinik und Poliklinik für Psychiatrie und Psychotherapie

    Greifswald, 17475

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

    Hamburg, 20246

  • Medizinische Hochschule Hannover, Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie

    Hanover, 30625

  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie

    Leipzig, 04103

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

    Lübeck, 23538

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

    Stralsund

Other trials in Germany

About this study

Official title: Simvastatin add-on to Escitalopram in Patients With Comorbid Obesity and Major Depression: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial

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.

Being tested
Simvastatin 40mg, Placebo oral tablet
Medical subject headings
Depressive Disorder, Major, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Simvastatin 40mgDrug

    Also called Zocor, C10AA01

    12 weeks 40 mg Simvastatin add-on

  • Placebo oral tabletDrug

    12 weeks Placebo add-on

Study groups in NCT04301271
Study groupRoleWhat they receive
SimvastatinExperimentalSimvastatin and Escitalopram
Receives: Drug: Simvastatin 40mg
PlaceboPlacebo comparatorPlacebo and Escitalopram
Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Secondary outcomes (10)

  1. MADRS-response

    Response is defined as 50% MADRS score reduction at week 12 from baseline.

    Measured: 12 weeks

  2. MADRS-remission

    Remission is defined as a MADRS score less than 10 at week 12.

    Measured: 12 weeks

  3. MADRS-MCID

    MADRS Minimal Clinically Important Difference represents the smallest improvement that is considered meaningful by the patient. Empirically, the MCID using the MADRS has been identified as a change from baseline between 1.6 - 1.9 at week 12.

    Measured: 12 weeks

  4. Change score in BDI-II (Beck Depression Inventory-II)

    The Beck Depression Inventory-II (BDI-II) is a 21-item validated instrument for the self-report of depressive symptoms, with individual item scores summed to yield a total possible BDI score that ranges from 0-63. BDI scores from 0-13 suggest absent to minimal depressive symptoms, from 14-19 mild symptoms, from 20-28 moderate symptoms, and from 29-63 severe symptoms.

    Measured: 12 weeks

  5. BDI-II-MCID

    BDI-II Minimal Clinically Important Difference represents the smallest improvement that is considered meaningful by the patient.

    Measured: 12 weeks

  6. Change score in PGIC (Patients' Global Impression of Change Scale)

    Participant rated instrument to measure participant's change in overall status on a scale of 0 to 7; range from 1 (very much improved) to 7 (very much worse).

    Measured: 12 weeks

  7. Change score in CGI-S (Clinicians' Global Impression of Severity of Illness)

    The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The CGI-S permits a global evaluation of the participant's condition at a given time.

    Measured: 12 weeks

  8. CGI-I (Clinicians' Global Impression of Improvement )

    Clinician rated instrument to measure clinicians' change in overall status on a scale of 0 to 7; range from 1 (very much improved) to 7 (very much worse).

    Measured: 12 weeks

  9. EQ-5D-3L (EuroQol-5 Dimensions-3 Levels Questionnaire)

    Generic instrument of quality of life related to health. It contains five dimensions of health (mobility, personal care, daily activities, pain / discomfort and anxiety / depression) and each of them has three levels of seriousness (without problems, some problems or moderate problems and serious problems).

    The second part of the EQ-5D is a Visual Analogue Scale (VAS) of 20 centimeters, millimeter, ranging from 0 (worse health status imaginable) to 100 (best imaginable health status). In it, the individual must mark the point in the vertical line that best reflects the assessment of their global health status today.

    Measured: 12 weeks

  10. SOFAS (Social and Occupational Functioning Assessment Scale)

    The SOFAS is a rating scale used to determine social functioning; range from 0-100. A higher score represents a better outcome.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2020
  2. Study start13 Aug 2020
  3. Primary completion6 Jun 2024
  4. Study completion6 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
161 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04301271
Sponsor's protocol ID
SIMCODE
Acronym
SIMCODE
Status last verified
Dec 2024
First submitted
6 Mar 2020
Last updated
9 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40465256

  • 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.

    PubMed 33262189

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Simvastatin 40mg in people with Depressive Disorder, Major and Obesity, run by Charite University, Berlin, Germany at 9 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change score in MADRS (Montgomery-Asberg-Depression Rating Scale) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04301271, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2024.

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