CompletedNCT02188121FITNESSUpdated Jan 30, 2023Results posted

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

A Phase 4 interventional study of Simvastatin and Losartan in Serious Mental Illness, Schizophrenia and Schizoaffective Disorder, sponsored by Mclean Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 89 Years. Per ClinicalTrials.gov, last updated 2023-01-30.

Sponsored by Mclean Hospital · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 227
Allocation: Randomized
Ages: 18 Years to 89 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

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

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In context

Cardiovascular Diseases

4,902 studies on the registry are indexed under Cardiovascular Diseases; 920 are open to participants now.

This study's enrollment of 227 is above the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.

Browse Cardiovascular Diseases studies →

Lead sponsor

Mclean Hospital is the lead sponsor of 181 studies on the registry; 32 are open to participants now.

Of its 14 completed or terminated interventional studies of FDA-regulated products, 10 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 89 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 227 participants (actual)

Study arms

Experimental
Statin and/or Angiotensin Receptor Blocker
Simvastatin 20mg PO daily and/or Losartan 25mg PO daily
Drug: Simvastatin · Drug: Losartan
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.

Interventions

DrugSimvastatin
3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors
DrugLosartan
Angiotensin II receptor antagonist

What researchers measure

Primary outcomes

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

Secondary outcomes

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

Other outcomes

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).
Time frame: 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.
Time frame: Baseline and 3, 6, 9, and 12 months
Change in Systolic Blood Pressure
Similar to secondary outcome measure but focusing on Systolic Blood Pressure
Time frame: Baseline and 3, 6, 9, and 12 months
Change in Hemoglobin A1C
Similar to secondary outcome measure but focusing on Hemoglobin A1c
Time frame: Baseline and 3, 6, 9, and 12 months
Change in Percent on Adequate Cardiovascular Prevention Care
Time frame: Baseline to 3 months
Change in Percent on Adequate Cardiovascular Prevention Care
Time frame: Baseline to 6 months
Change in Percent on Adequate Cardiovascular Prevention Care
Time frame: Baseline to 9 months
Mean Percentage of Follow up Time During Which Each Group is on Adequate Cardiovascular Prevention Care
Time frame: Baseline to 12 months

Results

Posted Nov 22, 2022

Participant flow

Participant flow — Overall Study
Milestone	Statin and/or Angiotensin Receptor Blocker	Usual Treatment
Started	99	105
Completed	79	78
Not completed	20	27

Outcome measures

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

Time frame:: Baseline to 12 months
Reported as:: Count of participants · Participants

Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)
Participants	Statin and/or Angiotensin Receptor Blocker	Usual Treatment
Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)	66	8

SecondaryChange in Low Density Lipoprotein Levels

Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c

Time frame:: Baseline to 12 months
Reported as:: Mean · mg/dL

Change in Low Density Lipoprotein Levels
mg/dL	Statin and/or Angiotensin Receptor Blocker	Usual Treatment
Baseline	100 (96 to 105)	106 (101 to 117)
12 months	86 (82 to 96)	100 (97 to 117)

Other pre-specifiedChange 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).

Time frame:: Baseline and 3, 6, 9, and 12 months