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

Fixed Dose Intervention Trial of New England Enhancing Survival in Serious Mental Illness Patients

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Major Depressive Disorder; Serious Mental Illness; Psychosis NOS
• Intervention / Treatment: Drug: Simvastatin; Drug: Losartan

Detailed Description

By design, all subjects in the Intervention arm will start by being under treatment. During the course of follow-up, we expect that some will stay consistently on treatment, some will discontinue treatment (become non-adherent), while others will make transitions on and off treatment in various patterns. In contrast, by design, subjects in the Usual Treatment (control) arm do not start on treatment; however, some will initiate treatment as a result of usual clinical care, e.g., primary care physician initiation. At any point we will be comparing two binary outcomes (on or off treatment) and will use standard methods for comparing two proportions to test statistical significance and get confidence intervals for the difference in the percent on treatment in the two arms. Participants who are ineligible for randomization will be followed similarly to participants in the Usual Treatment Arm, in a third, non-randomized group, which will be excluded from the primary analysis.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• • 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Statin and/or Angiotensin Receptor Blocker; Simvastatin 20mg PO daily and/or Losartan 25mg PO daily	Drug: Simvastatin; 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors; Drug: Losartan; Angiotensin II receptor antagonist
No Intervention: Usual treatment; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Low Density Lipoprotein Levels	Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c	Baseline to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Modified Framingham Score as a Summary Cardiovascular Risk Level	The outcome here is the difference in summary risk level changes (e.g., modified Framingham score) between our two study groups, i.e., do intervention subjects experience differential changes in cardiovascular risk levels compared to control subjects. This outcome will be continuously measured (but not necessarily normally distributed).	Baseline and 3, 6, 9, and 12 months
Change in Number of Distinct Cardiovascular Prevention Drugs Taken	Similar to primary outcome measure, but here we count the number of distinct cardiovascular prevention drugs taken by the patient as a continuous measure to reflect potential for partial treatment.	Baseline and 3, 6, 9, and 12 months
Change in Systolic Blood Pressure	Similar to secondary outcome measure but focusing on Systolic Blood Pressure	Baseline and 3, 6, 9, and 12 months
Change in Hemoglobin A1C	Similar to secondary outcome measure but focusing on Hemoglobin A1c	Baseline and 3, 6, 9, and 12 months
Change in Percent on Adequate Cardiovascular Prevention Care		Baseline to 3 months
Change in Percent on Adequate Cardiovascular Prevention Care		Baseline to 6 months
Change in Percent on Adequate Cardiovascular Prevention Care		Baseline to 9 months
Mean Percentage of Follow up Time During Which Each Group is on Adequate Cardiovascular Prevention Care		Baseline to 12 months

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Collaborators: Michael J. Gill Mental Health Clinic; The Massachusetts Mental Health Center; Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital; The Edinburg Center, Bedford MA
• Investigators: Principal Investigator: Dost Ongur, MD PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (Estimate): July 11, 2014

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Depressive Disorder; Cardiovascular Diseases; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Bipolar Disorder; Depressive Disorder, Major; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan; Simvastatin
• Other Study ID Numbers: 2014P001599

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No