Relief of Joint Pain
Conditions
Keywords
Aromatase Inhibitor, Breast Cancer, Arthralgia, Musculoskeletal symptoms, Joint pain
Brief summary
Significant Aromatase Inhibitor-associated toxicity, affects as many as 50% of patients with breast cancer leading to early discontinuation of this life-saving cancer treatment. No effective pharmacologic therapy has yet been identified for management of these symptoms, as many patients do not experience relief of symptoms with analgesic therapy. Vitamin B12, whether as injection or oral forms, has been used as a naturopathic product to provide relief for joint pain caused by arthritis. This effect has not been studied in the setting of Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS).
Detailed description
Primary Objectives: a. To assess whether daily oral Vitamin B12 decreases average joint pain in women with aromatase inhibitor-associated musculoskeletal symptoms (AIMSS), as measured at baseline, 6 weeks and at 12 weeks by the modified Brief Pain Inventory Short Form (BPI-SF). Secondary Objectives: 1. To investigate whether daily vitamin B12 improves functional quality of life as measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES); 2. To explore the impact of treatment on serum inflammatory cytokine levels (C Reactive Protein) with 12 weeks of treatment between baseline and 12 weeks.
Interventions
DIETARY_SUPPLEMENTVitamin B12
Vitamin B12 2500 micrograms sublingually per day over the course of 90 days (+/- 10 days)
Sponsors
Texas Tech University Health Sciences Center, El Paso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Vitamin B12 is to be taken sublingually on a daily basis for 90 days
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sign informed consent and Pain level \> 4 in the BPI scale, * Stage I-III
Exclusion criteria
* \<18 yrs * Stage IV * BPI Score \<4 * Zubrod score \>2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Average Joint Pain in Women With Aromatase Inhibitor-associated Musculoskeletal Symptoms (AIMSS) Compared to Baseline as Measured by the Brief Pain Inventory Short Form (BPI-SF). | Baseline and 90 days (+/- 10 days) | The Brief Pain Inventory - Short Form (BPI- SF) average pain score used. This item has a scale of 0 to 10 with 0 indicating No pain and 10 indicating Pain as bad as you can imagine We expect at least 20% improvement in BPI-SF pain scores. Participants were asked to rate worst pain an average pain within the last 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Worst Pain at the End of Treatment . | Baseline and 90 days (+/- 10 days) | Analysis of the data collected at baseline and at the end of treatment in the BPI-SF questionnaire. The Brief Pain Inventory - Short Form (BPI- SF) worst pain score used. This item has a scale of 0 to 10 with 0 indicating No pain and 10 indicating Pain as bad as you can imagine. Participants were asked to rate worst pain an average pain within the last 24 hours. |
| Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | Baseline and 90 days (+/- 10 days) | All of the items in this questionnaire have a 5 scale rating, from not at all (0) to very much (4). Outcomes were measured pre and post treatment. Version 4 of the FACT-ES contains 3 subscales with seven questions: Physical Well-Being (PWB) (score range 0-28), Functional Well-Being (FWB) (score range 0-28), and Social and Well-Being (SWB) (score range 0-28); Emotional Well-Being (EWB) (score range 0-24) with six questions, and the Endocrine Symptom Subscale (ESS) (score range 0-76) containing 19 questions. For all subscale a higher score represents better quality of life. |
| Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA). | Baseline and at 90 days (+/- 10 days) | Inflammatory markers were measured pre and post treatment. |
Participant flow
Recruitment details
we needed at least a total of 30 patients to achieve more than 85% power to detect the differences in BPI-SF pain scores relative to baseline using a two tailed paired t-test with 5% level of significance. After accounting for 15% dropouts, we estimated to include at least 35 patients in the study.
Pre-assignment details
IRB approved recruitment of 50 participants
Participants by arm
| Arm | Count |
|---|---|
| Arm I Oral Vitamin B12
Vitamin B12: Vitamin B12 2500 micrograms sublingually per day over the course of 90 days (+/- 10 days) | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 41 Participants |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 36 |
| other Total, other adverse events | 14 / 36 |
| serious Total, serious adverse events | 0 / 36 |
Outcome results
Primary
Percentage Change in Average Joint Pain in Women With Aromatase Inhibitor-associated Musculoskeletal Symptoms (AIMSS) Compared to Baseline as Measured by the Brief Pain Inventory Short Form (BPI-SF).
The Brief Pain Inventory - Short Form (BPI- SF) average pain score used. This item has a scale of 0 to 10 with 0 indicating No pain and 10 indicating Pain as bad as you can imagine We expect at least 20% improvement in BPI-SF pain scores. Participants were asked to rate worst pain an average pain within the last 24 hours.
Time frame: Baseline and 90 days (+/- 10 days)
Population: A total of forty-one patients were enrolled, five patients withdrew, leaving thirty-six patients to complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Percentage Change in Average Joint Pain in Women With Aromatase Inhibitor-associated Musculoskeletal Symptoms (AIMSS) Compared to Baseline as Measured by the Brief Pain Inventory Short Form (BPI-SF). | -33.8 Percentage change | Standard Deviation 34.1 |
p-value: <0.0001t-test, 1 sided
Secondary
Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES)
All of the items in this questionnaire have a 5 scale rating, from not at all (0) to very much (4). Outcomes were measured pre and post treatment. Version 4 of the FACT-ES contains 3 subscales with seven questions: Physical Well-Being (PWB) (score range 0-28), Functional Well-Being (FWB) (score range 0-28), and Social and Well-Being (SWB) (score range 0-28); Emotional Well-Being (EWB) (score range 0-24) with six questions, and the Endocrine Symptom Subscale (ESS) (score range 0-76) containing 19 questions. For all subscale a higher score represents better quality of life.
Time frame: Baseline and 90 days (+/- 10 days)
Population: postemneopausal women with ER + , Stages I-III breast cancer
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I | Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | SWB | 10.02 Percentage change | Standard Deviation 27.7 |
| Arm I | Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | EWB | 10.8 Percentage change | Standard Deviation 38.6 |
| Arm I | Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | PWB | 46.3 Percentage change | Standard Deviation 62.5 |
| Arm I | Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | FWB | 18 Percentage change | Standard Deviation 45 |
| Arm I | Percentage Change in Functional Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) | ESS | 15.6 Percentage change | Standard Deviation 19.6 |
p-value: 0.133t-test, 2 sided
Comparison: This analysis is comparing EWB before and after treatment.p-value: 0.056t-test, 2 sided
Comparison: This analysis is comparing PWB before and after treatment.p-value: <0.0001t-test, 2 sided
Comparison: This analysis is comparing FWB before and after treatment.p-value: 0.09t-test, 2 sided
Comparison: This analysis is comparing ESS before and after treatment.p-value: <0.0001t-test, 2 sided
Secondary
Percentage Change in Worst Pain at the End of Treatment .
Analysis of the data collected at baseline and at the end of treatment in the BPI-SF questionnaire. The Brief Pain Inventory - Short Form (BPI- SF) worst pain score used. This item has a scale of 0 to 10 with 0 indicating No pain and 10 indicating Pain as bad as you can imagine. Participants were asked to rate worst pain an average pain within the last 24 hours.
Time frame: Baseline and 90 days (+/- 10 days)
Population: Postmenopausal women with ER+ breast cancer, stages I-III on aromatase inhibitors and musculoskeletal pain (average pain level \> or=4 using BPI-SF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Percentage Change in Worst Pain at the End of Treatment . | -23.03 Percentage change | Standard Deviation 43.1 |
p-value: 0.0003t-test, 2 sided
Secondary
Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA).
Inflammatory markers were measured pre and post treatment.
Time frame: Baseline and at 90 days (+/- 10 days)
Population: postmenopasual women receiving AI
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Arm I | Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA). | HCys | -24.6 Percentage change | Standard Deviation 19.75 |
| Arm I | Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA). | MMA | -7.1 Percentage change | Standard Deviation 81.65 |
| Arm I | Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA). | B12 | 209.8 Percentage change | Standard Deviation 191.3 |
| Arm I | Percentage Change of Serum Levels of Vitamin B12, C-reactive Protein (CRP), Homoscyteine (HCys) and Methylmalonic Acid (MMA). | CRP | 64.2 Percentage change | Standard Deviation 298.5 |