Breast Cancer, Joint Pain
Conditions
Keywords
breast cancer, aromatase inhibitor, supportive care
Brief summary
Investigators are hoping to learn if glucosamine with chondroitin can help relieve joint pain/stiffness associated with aromatase inhibitors.
Detailed description
Due to early detection and improved treatments, women with breast cancer are living longer. The increase in breast cancer survival is largely due to the benefits of hormonal therapy, such as tamoxifen and aromatase inhibitors (AIs), for the treatment of hormone-sensitive breast cancer. Recent clinical trials have demonstrated that AIs are more effective than tamoxifen at reducing breast cancer recurrences. However, breast cancer patients receiving AIs have a higher incidence of osteoporosis, bone fractures and musculoskeletal symptoms, particularly joint pain and stiffness. Musculoskeletal pain, which occurs in up to 50% of patients treated with AIs, often does not respond to conventional pain medications, may lead to noncompliance, may cause major disability, and may interfere with quality of life. Many women are unable to tolerate these life-saving drugs because of severe joint pain, therefore, safe and effective treatments that alleviate these symptoms are needed.
Interventions
DRUGChondroitin
400mg chondroitin three times a day (TID) for twenty-four weeks
DRUGGlucosamine
500mg glucosamine TID for twenty-four weeks
Sponsors
Dawn L. Hershman
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>21 years. * Postmenopausal status defined as cessation of menses for \>1 year or follicle-stimulating hormone (FSH) \>20 milli-international units per milliliter or bilateral oophorectomy. * History of stage I, II or III hormone receptor-positive breast cancer, without metastatic disease. * Currently taking a third-generation aromatase inhibitor for at least 3 months. * Clinical symptoms of knee and/or hand joint pain and/or stiffness for at least 3 months prior to study entry. * Ongoing musculoskeletal pain/stiffness in hand and/or knee joints (50 or higher on the 100 point global assessment VAS) that started or increased since initiating aromatase inhibitor therapy, and has been present for at least 3 months. * Patients must agree to refrain from use of glucosamine and chondroitin from sources outside of this study. * If taking bisphosphonates, on a stable dose for at least 3 months and tolerating the dose. Patients must agree to refrain from initiating bisphosphonate use during the course of the study, therefore it is recommended that routine bone density testing be performed prior to enrollment or after completing trial. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Hemoglobin A1c \<8 within the last year. * Signed informed consent.
Exclusion criteria
* Use of glucosamine or chondroitin within the past three (3) months. * Concurrent medical/arthritic disease that could confound or interfere with evaluation of pain or efficacy. * History of significant collateral ligament, anterior cruciate ligament or meniscal injury of the index joint requiring surgery or non-weight bearing (requiring use of crutches or cane) for more than 3 weeks (minor ligamentous injury prior to 6 months is not an exclusion). * History of bone fracture or surgery of the afflicted knees and/or hands within 6 months prior to study entry. * Uncontrolled diabetes mellitus, defined as Hemoglobin A1c level of \> 8%. * History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the patient. * Allergy to, or history of significant clinical or laboratory adverse experience associated with acetaminophen, glucosamine or chondroitin sulfate. * Allergy to shellfish. * Inability to understand and complete study questionnaires including questions requiring a visual analog scale (VAS) response. * Inability to understand the study procedures and/or give written informed consent. * Alcohol use in excess of 3 mixed drinks/day. * Corticosteroid treatment was used or administered. * Aspirin (up to 325 mg/day) for cardiovascular reasons may be continued. * Intra-articular injection of hyaluronic acid or congeners into the study joint within 12 months. * Topical analgesics (e.g., capsaicin preparations) to the study joint, or any oral analgesics (e.g., opiates, tramadol; with the exception of ibuprofen and acetaminophen) within 2 weeks of baseline visit or during the study. * Implementation of any other medical therapy for arthritis within one month prior to entry. * Other medications, unrelated to the patient's joint pain/stiffness must have been used at a stable dosage for at least 1 month. In addition, it should be anticipated that the dose of the concomitant medication will be stable during the entire treatment period. * Participation in another clinical study with an investigational agent within the last 4 weeks. * Exposure to glucosamine within 3 months or chondroitin sulfate within 3 months of Baseline Visit. * Initiation of physical therapy or muscle conditioning program within 2 months prior to study entry. * Concurrent use of the following medications and dietary supplements. * Chronic therapy with tetracycline or tetracycline derivatives. * Other new complementary or alternative regimens for the treatment of osteoarthritis, including, but not limited to, acupuncture, topical creams, oral agents, and magnets.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC Score | Baseline and 24 weeks | This is to demonstrate improvement in knee and/or joint pain and/or stiffness. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. It is a self-administered questionnaire consisting of 24 items divided into 3 subscales. The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The sum of the scores for all three subscales gives a total WOMAC score which ranges from 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Countries
United States
Participant flow
Recruitment details
53 women were enrolled in this study at baseline, 16 dropped out before the week 24 assessment. in total, there were 39 evaluable participants.
Pre-assignment details
Of the 16 participants that dropped out of the study, 5 did so because of the number of pills, 8 due to adverse events and uncontrolled pain, and 3 dropped out due to other life events. 40 participants completed the 12 week assessment; 27 participants completed the 24 week assessment.
Participants by arm
| Arm | Count |
|---|---|
| Chondroitin and Glucosamine Postmenopausal breast cancer patients that have joint symptoms induced by aromatase inhibitors and are receiving chondroitin and glucosamine.
Chondroitin: 400mg chondroitin TID for twenty-four weeks
Glucosamine: 500mg glucosamine TID for twenty-four weeks | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | life events, pain | 11 |
Baseline characteristics
| Characteristic | Chondroitin and Glucosamine |
|---|---|
| Age, Customized 18 - 58 years | 23 Participants |
| Age, Customized 59 - 78 years | 24 Participants |
| Age, Customized > or = 79 | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment United States | 53 participants |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 53 |
| other Total, other adverse events | 51 / 53 |
| serious Total, serious adverse events | 0 / 53 |
Outcome results
Primary
Change in WOMAC Score
This is to demonstrate improvement in knee and/or joint pain and/or stiffness. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. It is a self-administered questionnaire consisting of 24 items divided into 3 subscales. The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The sum of the scores for all three subscales gives a total WOMAC score which ranges from 0-96. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: Baseline and 24 weeks
Population: At completion of the study, there were 39 evaluable subjects (this excludes participants who were not available for follow-up) out of the 53 enrolled.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chondroitin and Glucosamine | Change in WOMAC Score | 24.9 Score on a scale | Standard Deviation 21.4 |
Comparison: This statistical analysis measures whether there is a statistically significant change, at the 5% significance level, between the mean WOMAC score among study participants at baseline and at week 24.p-value: 0.004t-test, 2 sided