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

• ClinicalTrials.gov Identifier: NCT02188121
• Recruitment Status: Active, not recruiting
• First Posted: July 11, 2014
• Last Update Posted: October 8, 2019
• 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
• Information provided by (Responsible Party): Dost Ongur, Mclean Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Serious Mental Illness; Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Cardiovascular Disease; Major Depressive Disorder; Psychosis NOS	Drug: Simvastatin; Drug: Losartan	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 268 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fixed Dose Intervention Trial of New England Enhancing Survival in Serious Mental Illness Patients
• Study Start Date: February 2015
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: October 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in percentage of participants on adequate cardiovascular prevention care (defined as taking a statin and angiotensin medication) [ Time Frame: Baseline to 12 months ]

Secondary Outcome Measures :

1. Change in Modified Framingham Score as a summary cardiovascular risk level [ Time Frame: Baseline and 3, 6, 9, and 12 months ]
   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).

Other Outcome Measures:

1. Change in number of distinct cardiovascular prevention drugs taken [ Time Frame: Baseline and 3, 6, 9, and 12 months ]
   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.
2. Change in Low Density Lipoprotein levels [ Time Frame: Baseline and 3, 6, 9, and 12 months ]
   Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c
3. Change in Systolic Blood Pressure [ Time Frame: Baseline and 3, 6, 9, and 12 months ]
   Similar to secondary outcome measure but focusing on Systolic Blood Pressure
4. Change in Hemoglobin A1C [ Time Frame: Baseline and 3, 6, 9, and 12 months ]
   Similar to secondary outcome measure but focusing on Hemoglobin A1c
5. Change in percent on adequate cardiovascular prevention care [ Time Frame: Baseline to 3 months ]
6. Change in percent on adequate cardiovascular prevention care [ Time Frame: Baseline to 6 months ]
7. Change in percent on adequate cardiovascular prevention care [ Time Frame: Baseline to 9 months ]
8. Mean percentage of follow up time during which each group is on adequate cardiovascular prevention care [ Time Frame: Baseline to 12 months ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

McLean Hospital

Belmont, Massachusetts, United States, 02478

Sponsors and Collaborators

Mclean Hospital

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 Documents (Full-Text)

Documents provided by Dost Ongur, Mclean Hospital:

Statistical Analysis Plan  [PDF] February 10, 2018

Study Protocol  [PDF] February 21, 2018

More Information

• Responsible Party: Dost Ongur, Chief of Psychotic Disorders Division at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT02188121
• Other Study ID Numbers: PHS IRB pending
• First Posted: July 11, 2014
• Last Update Posted: October 8, 2019
• Last Verified: October 2019

Additional relevant MeSH terms:

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