Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

Phase 2

Completed

Conditions: Anxiety Disorder
Depression
Recurrent Breast Cancer
Stage IA Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IB Breast Cancer
Stage IIIC Breast Cancer

Interventions: Drug: minocycline hydrochloride
Other: placebo
Other: laboratory biomarker analysis
Other: Questionnaire administration

Registration Number: NCT02203552

Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary: This randomized clinical trial studies how well minocycline hydrochloride works in reducing chemotherapy induced depression and anxiety in patients with stage I-III breast cancer. Minocycline hydrochloride may prevent changes in memory and thinking and improve the quality of life of breast cancer patients receiving chemotherapy.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate anxiety and depression in women with stages I-III breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline (minocycline hydrochloride) or placebo.

II. To evaluate markers of neuro-inflammation as assessed by blood based inflammatory cytokines and C11-choline positron emission tomography (PET) in women with stages I-III breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline or placebo.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally (PO) twice daily (BID) for 9 weeks.

ARM II: Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks.

After completion of study treatment, patients are followed up for 6 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 56

Inclusion Criteria

Women diagnosed with breast cancer stages I-III initiating first line adjuvant or neoadjuvant doxorubicin hydrochloride (DOX) chemotherapy
Postmenopausal defined as amenorrhea > 12 months or follicle stimulating hormone (FSH) and estradiol in institutional postmenopausal range
Ability to understand English and read and write at the 8th grade level and give a written informed consent document
For additional cohort, women with breast cancer stages I-III who currently on or within 18 months of completing first line adjuvant or neoadjuvant DOX chemotherapy or other chemotherapy for breast cancer.

Exclusion Criteria

Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease, with the exception of osteoarthritis and fibromyalgia
Concurrent other malignancy or metastatic malignancy of any kind
Reported diagnosis of major depression or anxiety disorder prior to breast cancer (BC) diagnosis
Currently prescribed psychotropic medications including anti-depressants
Known bleeding disorders
History of diabetes mellitus, heart disease or stroke
Current use of warfarin or other anticoagulants
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hypertension, or psychiatric illness/social situation that would limit compliance with study requirements
Pregnant or nursing women
Concurrent use of daily full dose aspirin (>= 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization
Unable to give informed consent
Tetracycline allergy
Any contraindication to magnetic resonance imaging (MRI)/PET examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia; (however, this portion is optional and if patient is otherwise eligible, can enroll in study without participating in imaging study)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (minocycline hydrochloride)	minocycline hydrochloride	Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
Arm I (minocycline hydrochloride)	laboratory biomarker analysis	Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
Arm I (minocycline hydrochloride)	Questionnaire administration	Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
Arm II (placebo)	placebo	Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
Arm II (placebo)	laboratory biomarker analysis	Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
Arm II (placebo)	Questionnaire administration	Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.

Primary Outcome Measures

Name	Time	Method
Changes in Center for Epidemiological Studies Depression Scale (CES-D) Scores	Baseline to 9 weeks	CES-D scale a short self-reported scaled designed to measure depressive symptomology in the general population. At baseline, depressive symptom severity will be assessed using the CES-D instrument. Evaluation of the patients assessment if suicidal ideation is reported at baseline. A value of 0, 1, 2, or 3 is assigned to a response depending upon positively or negatively. The subject will be withdrawn from the administrated serially every cycle starts on protocol during clinic visits (Patients will self-administer forms given out by research coordinator).The internal consistency for the STAI is .95; higher scores indicate greater anxiety.41 The internal consistency for the CES-D is approximately .85 among BC patients,42 and an important benefit of using this scale in medical studies is that it is relatively unaffected by physical symptoms. Total scores range from 0-60 with higher scores reflecting greater depressive symptoms. The 95% confidence intervals of the depression change from b
Changes in the State Trait Anxiety Index (STAI) Scores	Baseline to 9 weeks	The mean changes over time in State Trait Anxiety Index (STAI) scores from baseline to the end of study for the two study groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. The range of possible scores for form Y of the STAI varies from a minimum score of 20 to a maximum score of 80. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).The 95% confidence intervals of the change in the primary outcome measures from baseline to the end of study and the differences between the treatment and placebo groups will be estimated based on the models.

Secondary Outcome Measures

Name	Time	Method
Changes in Hamilton Anxiety Rating Scale Scores	Baseline to 9 weeks	The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.
Changes in Hamilton Rating Scale for Depression Scores	Baseline to 9 weeks	The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.
Changes in Inflammatory Blood Markers	Baseline to 6 months	Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.
Changes in the PET/MRI Measures	Baseline to 6 months	Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.

Trial Locations

Locations (1): Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States