Telmisartan Pilot Study on Treatment Resistant Schizophrenia

Study Overview
=================
Brief Summary
-----------------
This study is a 4-week pilot study for subjects with Schizophrenia or Schizoaffective Disorder who have not experienced a significant relief of symptoms from current anti-psychotic medication. The Investigators hypothesize that 4 weeks of telmisartan at 80mg daily will alter blood biomarkers for inflammation and oxidative stress after 4 weeks treatment.

Official Title
-----------------
An Open-label Feasibility Trial of Adjunctive Telmisartan in Patients With Treatment Resistant Schizophrenia

Conditions
-----------------
Schizophrenia, Schizo Affective Disorder, Treatment-resistant Schizophrenia

Intervention / Treatment
-----------------
* Drug: Telmisartan Pill


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-65 years inclusive. Primary diagnosis of Schizophrenia or Schizoaffective Disorder established by a structured psychiatric evaluation (MINI) based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) criteria. A Positive and Negative Syndrome Scale (PANSS) (Kay et al 1987) total score ≥ 70 with a score of > 4 on two or more of the following PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. A score of ≥4 on the Clinical Global Impression-Severity (CGI-S) (Guy, 1976). Must have ongoing antipsychotic treatment for at least 8 weeks, with a stable dose for at least 4 weeks. Subjects who have failed to achieve clinically-recognized symptom reduction to at least 1 marketed antipsychotic agent at a therapeutic dose for ≥ 8 weeks during the past 12 months, will be eligible. Women of childbearing potential must have a negative pregnancy test performed at screening visit prior to receiving the study medication. Women enrolled in this trial must use single barrier contraception. Exclusion Criteria: Psychiatrically unstable. Subjects with any clinically significant abnormalities as determined by medical history, physical exam, clinical and lab evaluation suggestive of an underlying disease state that may, in the opinion of the investigator, confound the results of study, increase risk to the subject, or lead to difficulty complying with the study plan. Current insulin treatment for diabetes. History of immunosuppression. Current or recent radiation or chemotherapy treatment for cancer. Chronic use of steroids (except local use or inhaler). Pregnancy or breastfeeding. Women who are planning to become pregnant. Use of diuretics, ACE inhibitors, spironolactone, potassium supplements, digoxin or warfarin because the possible drug-drug interaction with telmisartan. Tested positive for the urine drug screen. Subjects at imminent risk of suicide or injury to self or others, as per the opinion of the investigator, or history of significant suicide attempt within the last 6 months as per the Columbia Suicide Severity Rating Scale (C-SSRS). Subjects that have taken an investigational drug or taken part in a clinical trial within 30 days prior to screening. Subjects with a current (within the last 3 months) DSM-V diagnosis of alcohol or substance use disorder (excluding nicotine and caffeine) as established by the clinical assessment (MINI) at the screening visit will be excluded. Any other reason that, in the opinion of the investigator, would compromise patient safety or integrity of the study. Subjects with the lab values defined as exclusionary safety values.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan Pill<br>Subjects will start telmisartan 40mg once a day during week 1; the dose will be increased to 80mg (target dose) or as tolerated during the remaining three weeks. | Drug: Telmisartan Pill<br>* telmisartan 40mg once a day during week 1; the dose will be increased to 80mg (target dose) or as tolerated during the remaining three weeks.<br>* Other names: Micardis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Blood Levels of Tumor Necrosis Factor Alpha | Levels at week 4 minus levels at baseline | Baseline (week 0) to 4 weeks after initial dose | 
| Changes in Blood Levels of Glutathione | Levels at week 4 minus levels at baseline | Baseline (week 0) to 4 weeks after initial dose | 
| Changes in Blood Levels of Interleukin-6 | Levels at week 4 minus levels at baseline | Baseline (week 0) to 4 weeks after initial dose | 
| Changes in Blood Levels of High Sensitivity C-Reactive Protein | Levels at week 4 minus levels at baseline | Baseline (week 0) to 4 weeks after initial dose |