Cardiovascular Biomarkers and Quetiapine in Depression and Anxiety Patients

• ClinicalTrials.gov Identifier: NCT00951483
• Recruitment Status: Completed
• First Posted: August 4, 2009
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016
• Sponsor: Loyola University
• Information provided by (Responsible Party): Angelos Halaris, Loyola University

Study Description

Brief Summary:

No suitable treatment has been identified to reverse and ideally prevent, the cardiovascular disease risk associated with depression and anxiety. The purpose of this study is to determine if quetiapine treatment of depression can reverse the signs of arterial stiffening that often occurs in depression and anxiety, and which are believed to be risk factors for future heart disease.

Condition or disease	Intervention/treatment	Phase
Depression; Anxiety	Drug: Quetiapine-XR	Phase 4

Detailed Description:

The evidence that depressive and anxiety disorders confer a high relative risk (RR) for cardiovascular disease (CVD) development is clear and compelling. A cadre of inflammation, platelet activation and other biomarkers of endothelial dysfunction strongly suggest multiple and possibly interrelated mechanisms underlying this co-morbidity. Early detection of the vulnerability to develop CVD has become an urgent health issue. However, detection alone of vulnerability without proper therapeutic intervention aimed at reversing it, is merely of scientific interest. The evidence to date that antidepressant drugs, while highly efficacious in restoring euthymia, may not normalize the biomarkers of CVD vulnerability. Hence, there is a need to identify other pharmacologic interventions for depression. Quetiapine, due to its unique molecular structure and unique pharmacological profile, belongs to none of the known classes of antidepressants. However, quetiapine clearly has antidepressant and anti-anxiety efficacies. Now, we propose to explore whether quetiapine can reverse those pathophysiological changes occurring in mixed depression/anxiety that have been linked causally to the development of CVD. Accordingly, the primary purpose of this study is to compare C-Reactive Protein between the treatment and healthy control groups at 12 weeks post treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Cardiovascular Biomarkers During Quetiapine Treatment of Depression
• Study Start Date: July 2009
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: October 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention Cohort; Patients will undergo baseline psychological and laboratory tests then receive Quetiapine-XR(Seroquel-XR) with flexible dosing at the discretion of the treating physician based on clinical response and tolerability. The dose range will be from 50-300mg. The total duration of the treatment will be 12 weeks.	Drug: Quetiapine-XR; Quetiapine-XR (Seroquel-XR) 50-300mg daily for 12 weeks.; Other Name: Seroquel
No Intervention: Healthy Control; Participants without major depressive disorder or anxiety are enrolled as a comparison group without intervention.

Outcome Measures

Primary Outcome Measures :

1. C-Reactive Protein at 12 Weeks [ Time Frame: 12 weeks ]
   To compare C-Reactive Protein between the treatment and healthy control groups at 12 weeks post treatment.

Secondary Outcome Measures :

1. Change in Hamilton Rating Scale for Depression With Seven Items (HAM-D-7) [ Time Frame: Baseline and 12 weeks ]
   The seven item Hamilton Rating Scale for Depression (HAMD-7) is an objective assessment of depression administered by a trained rater. This version allows scores to range from 0 to 22, where higher scores indicate worsening mood.
2. Change in Hamilton Rating Scale for Depression With 17 Items (HAM-D-17) [ Time Frame: Baseline and 12 weeks ]
   The 17-item Hamilton Rating Scale for Depression (HAMD-17) is an objective assessment of depression administered by a trained rater. This version allows scores to range from 0 to 52, where higher scores indicate worsening mood.
3. Change in Hamilton Rating Scale for Depression With 21 Items (HAMD-21) [ Time Frame: Baseline and 12 weeks ]
   The 21-item Hamilton Rating Scale for Depression (HAMD-21) is an objective assessment of depression administered by a trained rater. This version allows scores to range from 0 to 52, where higher scores indicate worsening mood.
4. Change in Hamilton Rating Scale for Anxiety (HAM-A) [ Time Frame: Baseline and 12 weeks ]
   The 14-item Hamilton Rating Scale for Anxiety (HAM-A) is an objective assessment of anxiety administered by a trained rater. This version allows scores to range from 0 to 56, where higher scores indicate worsening anxiety.
5. Change in Beck Depression Inventory (BDI) [ Time Frame: Baseline and 12 weeks ]
   The 21-item Beck Depression Inventory (BDI) is a subjective self-report assessment of depression. This version allows scores to range from 0 to 63, where higher scores indicate worsening mood.
6. Change in 14-item Perceived Stress Scale (PSS-14) [ Time Frame: Baseline and 12 weeks ]
   The 14-item Perceived Stress Scale (PSS-14) is a subjective self-report assessment of stress. Each item is rated on a five point frequency scale ranging from 0 = never experiencing the stress symptom to 4 = Very often experiencing the stress symptom. Scores range from 0 to 56, where higher scores indicate higher stress.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• A diagnosis of Major Depressive Disorder (MDD), first episode or recurrent, by Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) requiring treatment. The index episode must be at least 14 days of persistent symptoms. If first episode, patients must not have been previously treated. If recurrent, must not be receiving treatment for the recurrence.
• Females and males 20-65 years of age
• Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at time of enrolment
• Able to understand and comply with the requirements of the study

Exclusion Criteria:

• Females who are pregnant, lactating, breast feeding or on oral contraceptives
• Any DSM-IV Axis I disorder not defined in the inclusion criteria except MDD co-morbid with generalized anxiety disorder (GAD)
• Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• Known intolerance or lack of response to quetiapine (Seroquel) as judged by the investigator
• Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
• Use of any of the following cytochrome P450 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
• Concomitant use of any other antidepressant, anxiolytic, or antipsychotic agent
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before the study begins
• Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
• History of heavy smoking within the preceding 6 months
• Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
• Restrictions prior to blood drawings: Aspirin (previous 240 hours), antihistamines (previous 72 hours), Tylenol (previous 72 hours), Vitamin C or E (previous 72 hours), sleeping pills (previous 72 hours), caffeinated beverages (8 hours), physical exertion (8 hours) and tobacco products (2 hours).
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator
• Involvement in the planning and conduct of the study
• Previous enrolment in the present study.
• Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements

• A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:

  • Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%.
  • Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
  • Not under physician care for DM
  • Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
  • Physician responsible for patient's DM care has not approved patient's participation in the study

Contacts and Locations

Locations

United States, Illinois

Loyola University Health System

Maywood, Illinois, United States, 60153

Sponsors and Collaborators

Loyola University

Investigators

• Principal Investigator: Angelos Halaris, MD, PhD; Loyola University

More Information

• Responsible Party: Angelos Halaris, Professor, Loyola University
• ClinicalTrials.gov Identifier: NCT00951483
• Other Study ID Numbers: 201880
• First Posted: August 4, 2009
• Results First Posted: October 24, 2016
• Last Update Posted: October 24, 2016
• Last Verified: August 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Angelos Halaris, Loyola University:

Cardiovascular Biomarkers; Depression; Quetiapine

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Quetiapine Fumarate; Antidepressive Agents; Psychotropic Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs