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

Randomized Placebo Controlled Study of Minocycline for Amelioration of Chemotherapy Induced Affective Disorders

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.

Study Overview

• Status: Completed
• Conditions: Depression; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Anxiety Disorder; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIIC Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Drug: minocycline hydrochloride; Other: laboratory biomarker analysis; Other: Questionnaire administration; Other: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (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.	Drug: minocycline hydrochloride; 100 mg bid given by mouth for 9 weeks; Other Names: Minocin; Dynacin; Minomax; Minomycin; Other: laboratory biomarker analysis; Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.; Other Names: Correlative studies; special studies; Other: Questionnaire administration; The CES-D and STAI will be administrated weekly.; Other Names: Ancillary studies
Placebo Comparator: Arm II (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.	Other: laboratory biomarker analysis; Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.; Other Names: Correlative studies; special studies; Other: Questionnaire administration; The CES-D and STAI will be administrated weekly.; Other Names: Ancillary studies; Other: placebo; Placebo given by mouth for 9 weeks; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Center for Epidemiological Studies Depression Scale (CES-D) Scores	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	Baseline to 9 weeks
Changes in the State Trait Anxiety Index (STAI) Scores	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.	Baseline to 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Hamilton Anxiety Rating Scale Scores	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.	Baseline to 9 weeks
Changes in Hamilton Rating Scale for Depression Scores	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.	Baseline to 9 weeks
Changes in Inflammatory Blood Markers	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.	Baseline to 6 months
Changes in the PET/MRI Measures	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.	Baseline to 6 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Bhuvaneswari Ramaswamy, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2015
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: July 28, 2014
• First Submitted That Met QC Criteria: July 28, 2014
• First Posted (Estimated): July 30, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Mental Disorders; Neoplasms by Site; Neoplasms; Behavioral Symptoms; Mood Disorders; Skin Diseases; Breast Diseases; Anxiety Disorders; Depression; Depressive Disorder; Breast Neoplasms; Anti-Bacterial Agents; Anti-Infective Agents; Minocycline
• Other Study ID Numbers: OSU-13165; NCI-2014-00851 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No