Fixed Dose Intervention Trial of New England Enhancing Survival in SMI Patients

NCT02188121 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2014P001599
• Study Type: interventional
• Target: 227
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with severe mental illness (SMI) die younger than persons in the general population. Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient adherence are central problems to reducing cardiovascular risks for patients with SMI. To address these problems, we propose to conduct a multi-site, open-label, randomized controlled trial comparing an initial treatment strategy of free, fixed-doses of two generic, cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental health clinics versus usual treatment. The study will include adult patients (18+ years old) with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or psychosis not otherwise specified (NOS) who have received 2GAs treatment within the past six months from within four mental health clinics in the Boston area. We have three aims: 1) to compare the proportions of subjects in each arm who are receiving cardiovascular drug treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels, accounting for variation in adherence over time, using causal inference techniques to estimate the per-protocol effect of the intervention. Our three aims examine whether this low cost, streamlined treatment strategy increases the numbers of subjects receiving cardiovascular prevention therapy and improves cardiovascular risk levels. We will follow subjects for 12 months, and collect interview and biometric data at baseline and over the following 12 months. Subjects will have the option to continue for another 12 months, during which we will continue to collect interview and biometric data, but will not prescribe cardiovascular medications. This population-based initial treatment strategy could be an effective and efficient approach for overcoming traditional barriers to cardiovascular disease prevention within the SMI population. Findings from this study will inform efforts to improve care and outcomes, and to enhance survival for patients with severe mental illness.

Conditions

Serious Mental Illness; Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Cardiovascular Disease; Major Depressive Disorder; Psychosis NOS

Outcome Measures

Primary Outcomes (1)

• Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)

  Baseline to 12 months

Secondary Outcomes (1)

• Change in Low Density Lipoprotein Levels

  Baseline to 12 months

Other Outcomes (8)

• Change in Modified Framingham Score as a Summary Cardiovascular Risk Level

  Baseline and 3, 6, 9, and 12 months

• Change in Number of Distinct Cardiovascular Prevention Drugs Taken

  Baseline and 3, 6, 9, and 12 months

• Change in Systolic Blood Pressure

  Baseline and 3, 6, 9, and 12 months

Study Arms (2)

Statin and/or Angiotensin Receptor Blocker

EXPERIMENTAL

Simvastatin 20mg PO daily and/or Losartan 25mg PO daily

Drug: Simvastatin; Drug: Losartan

Usual treatment

NO INTERVENTION

We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize "usual treatment". We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.

Interventions

Simvastatin DRUG

3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors

Statin and/or Angiotensin Receptor Blocker

Losartan DRUG

Angiotensin II receptor antagonist

Statin and/or Angiotensin Receptor Blocker

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Incident or prevalent cases: schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or psychosis NOS (chart diagnosis).
• Age 18 years and older.
• Recent treatment with a standing 2GA, e.g., receiving a standing 2GA in the past 6 months.
• Concomitant psychotropic medications will be allowed.
• Ongoing treatment of their mental illnesses at one of four study mental health clinics, defined as entering one of the two-year First Episode Clinic treatment programs as a de novo patient (new disease) or having been diagnosed \>2 years ago and had at least six visits in the past 12 months (prevalent disease).

You may not qualify if:

• Unstable/active disease or potential contraindications with both study medications, e.g., diabetes, unstable angina or recent acute coronary syndrome, pregnancy, very high risk factors on the screening labs (e.g., A1c\>7%), renal failure, liver failure, or both statin and angiotension drug contraindications.
• Unable to provide informed consent, e.g., has dementia, developmental disability, other cognitive disorder, or fails screening mini-mental status exam (subjects with guardians may participate with guardian consent)
• Receiving active cardiovascular treatment, defined as receiving both a statin or ARB in the past three months.

Sponsors & Collaborators

• Mclean Hospital: lead
• Michael J. Gill Mental Health Clinic: collaborator
• Massachusetts Mental Health Center: collaborator
• Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital: collaborator
• The Edinburg Center: collaborator

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

Related Publications (1)

• Chouinard VA, Price M, Forte S, Prete S, Heinrich H, Smith SN, Fung V, Hsu J, Ongur D. Baseline Cardiovascular Risk Factors in Patients With Severe Mental Illness (SMI) and Second Generation Antipsychotic Use From the Fixed Dose Intervention Trial of New England Enhancing Survival in SMI (FITNESS). J Clin Psychiatry. 2025 Jan 8;86(1):24m15392. doi: 10.4088/JCP.24m15392.

  PMID: 39832344 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Bipolar Disorder; Cardiovascular Diseases; Depressive Disorder, Major; Mental Disorders

Interventions

Simvastatin; Losartan

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Mood Disorders; Depressive Disorder

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Dr. Dost Ongur
• Organization: McLean Hospital

dongur@partners.org

617 855 3922

Study Officials

• Dost Ongur, MD PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Psychotic Disorders Division at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School

Study Record Dates

• First Submitted: July 8, 2014
• First Posted: July 11, 2014
• Study Start: February 1, 2015
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2021
• Last Updated: January 30, 2023
• Results First Posted: November 22, 2022

Record last verified: 2023-01

Locations

US (1)