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Trial of Oral Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias

Primary Purpose

Breast Neoplasm Female, Arthralgia

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Hyaluronic Acid (HA)

Placebo

About this trial

This is an interventional supportive care trial for Breast Neoplasm Female focused on measuring Aromatase Inhibitors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria

Age ≥ 18 years old.
Had been taking anastrazole or letrozole, and discontinued it within the past 90 days due to pain and/or stiffness. The AI-related pain/stiffness must have resolved.
Prior tamoxifen use is allowed.
A prior switch from exemestane is allowed.
Women who have undergone a total mastectomy or breast conserving surgery for Stage 0-3 breast cancer +/- chemotherapy, +/- antiHer2Neu therapy, +/- radiotherapy.
Must have ER and/or PR positive tumors.
Women who are postmenopausal by the presence of natural amenorrhea ≥ 12 months or by ovarian ablation (bilateral oophorectomy, radiation, or administration of a gonadotropin-releasing hormone agonist).
Eastern Cooperative Oncology Group Performance Score (ECOG PS) 0-3 (Appendix II).
Patients may or may not be taking non-opioid analgesics.
Adequate renal and hepatic function:
i) Include only subjects with AST and ALT < 2.0 × ULN; AP < 1.5 × ULN; total bilirubin < 1.2 × ULN ii) Include only subjects with as calculated creatinine clearance (CrCl) > 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen (BUN) < 1.5 × upper limit of normal (ULN)
Written informed consent from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria

Presence of residual or recurrent cancer.
Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
Consumption of HA-containing supplements in the four weeks prior to study.
Known allergy to microcrystalline cellulose or HA. Any questionable reaction to injected HA will be thoroughly investigated.
Prolonged systemic corticosteroid treatment, except for topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops or local insertion (i.e., intra-articular). A short duration of systemic corticosteroids is allowed but not within 30 days prior to registration.
Self-reported compliance issues and lack of regular prescription filling.
Previous diagnosis of fibromyalgia and/or rheumatoid arthritis.

Sites / Locations

Indiana University Health North Hospital
Indiana University Health Hospital
Indiana University Health Melvin and Bren Simon Cancer Center
Spring Mill Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Hyaluronic Acid

Placebo

Arm Description

Subjects in this arm will be given 100 mg of hyaluronic acid in capsule form. Subject in this arm will be asked to 1 capsule take twice daily for 26 weeks.

Subjects in this arm will be given a placebo comparator capsule that is identical to the hyaluronic capsule containing microcrystalline cellulose as the sole ingredient. Subjects in this arm will be asked to take 1 capsule twice daily for 26 weeks.

Outcomes

Primary Outcome Measures

Difference in mean change in joint pain between HA and placebo groups

As measured by the Brief Pain Inventory - Short Form (BPI-SF) questions #3-#6, #9A-G. This 14-item questionnaire was developed for use in patients with cancer that uses a scale from 0 to 10 to assess worst pain, pain severity, and pain interference over the past week. The first 8 items have to do with the severity of the pain, and the remaining 7 items ask about how the pain has affected function.

Secondary Outcome Measures

Incidence of treatment-emergent adverse events (i.e. safety and tolerability of HA)

Summary of adverse events as measured by CTCAE v4.0

Difference in mean joint symptoms between HA and placebo groups

As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) scores. This questionnaire assesses the three domains of pain, stiffness, and physical function in the lower extremities over the past 7 days. It is scored from 0 to 100, with higher scores indicating worse symptoms.

Difference in mean joint function between HA and placebo groups

As measured by Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH) scores. This 11-item instrument assesses physical function and symptoms in patients with musculoskeletal disorders of the upper limbs. It is a questionnaire scored from 1 to 5, with the higher score indicating worse symptoms, and there is a validated method to calculate a single Disability/Symptom Score.

Difference in mean quality of sleep between HA and placebo groups

As measured by Pittsburgh Sleep Quality Index (PSQI) scores. This an 18-item instrument produces a global sleep-quality score and the following component scores: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medications, and daytime dysfunction.

Difference in global change between HA and placebo groups

As measured by Patient's Global Impression of Change scale (PGIC) scores

Difference in mean change in WOMAC subscale 1 scores between HA and placebo groups

As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) subscale 1 scores. As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) scores. This questionnaire assesses the three domains of pain, stiffness, and physical function in the lower extremities over the past 7 days. It is scored from 0 to 100, with higher scores indicating worse symptoms.

Difference in mean change in WOMAC subscale 2 scores between HA and placebo groups

As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) subscale 2 scores. As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) scores. This questionnaire assesses the three domains of pain, stiffness, and physical function in the lower extremities over the past 7 days. It is scored from 0 to 100, with higher scores indicating worse symptoms.

Difference in mean change in WOMAC subscale 3 scores between HA and placebo groups

As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) subscale 3 scores. As measured by Western Ontario and McMaster osteoarthritis index (WOMAC) scores. This questionnaire assesses the three domains of pain, stiffness, and physical function in the lower extremities over the past 7 days. It is scored from 0 to 100, with higher scores indicating worse symptoms.

Time to discontinuation of second aromatase inhibitor due to AIMSS between HA and placebo groups

As measured by patient self-report of mediation compliance (medication diary) and chart review

Proportion of patients that remain on second aromatase inhibitor between HA and placebo groups

As measured by patient self-report of mediation compliance (medication diary) and chart review

Rate of 90% compliance between HA and placebo groups

As measured by patient self-report of mediation compliance (medication diary)

Mean frequency of as needed analgesia between HA and placebo groups

As measured by patient self-report of mediation compliance (medication diary)

Full Information

NCT ID

NCT03384095

First Posted

December 18, 2017

Last Updated

December 30, 2018

Sponsor

Erin Newton

Collaborators

Indiana University, NOW Foods

1. Study Identification

Unique Protocol Identification Number

NCT03384095

Brief Title

Trial of Oral Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias

Official Title

Single Center, Placebo-Controlled Trial of Oral High-Molecular Weight Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias

Study Type

Interventional

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Withdrawn

Why Stopped

study abandoned prior to opening to accrual or study start

Study Start Date

December 14, 2018 (Actual)

Primary Completion Date

December 14, 2018 (Actual)

Study Completion Date

December 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Erin Newton

Collaborators

Indiana University, NOW Foods

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a single center, double-blinded, placebo-controlled, randomized Phase II trial to determine whether oral hyaluronic acid will prevent aromatase inhibitor (AI)-associated arthralgias. Subjects must have ER/PR-positive breast cancer tumor with history of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) which resolved after cessation of their AI (anastrazole or letrozole) within 90 days of enrollment. Subjects will be stratified by initial AI, thus within each initial AI, subjects will be randomized to receive either the experimental treatment (hyaluronic acid) or placebo. Subjects will begin the assigned treatment for 2 weeks prior to transitioning to the second AI. Evaluations will be taken at baseline, 6 weeks (1 month on study drug and AI), 14 weeks (3 months on study drug and AI), and at 26 weeks (6 months on study drug and AI). Treatment with hyaluronic acid and placebo will last for 26 weeks total.

Detailed Description

Primary Objective To determine whether oral HA will prevent AI-induced arthralgias and preserve physical function. Secondary Objectives To explore whether oral HA will have an acceptable safety and tolerability profile. To determine whether oral HA will prevent other AI associated symptoms as assessed by patient reported outcomes (PRO's). To assess how many of the subjects are 90% compliant with taking the HA as directed. Exploratory Objective To determine if mi486, (a microRNA enriched in skeletal muscle) and other biomarkers associated with AIMSS (TNF, IL-6, IL-17) vary with the administration of HA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasm Female, Arthralgia

Keywords

Aromatase Inhibitors

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hyaluronic Acid

Arm Type

Experimental

Arm Description

Subjects in this arm will be given 100 mg of hyaluronic acid in capsule form. Subject in this arm will be asked to 1 capsule take twice daily for 26 weeks.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Hyaluronic Acid (HA)

Intervention Description

Dosage form: hyaluronic capsules; Dose: 100 mg; Frequency: twice daily; Duration: 26 weeks

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Dosage form: microcrystalline cellulose (MCC) capsules; Dose: approx. 100 mg (determined by weight of HA counterpart); Frequency: twice daily; Duration: 26 weeks

Primary Outcome Measure Information:

Title

Difference in mean change in joint pain between HA and placebo groups

Description

Time Frame

14 weeks

Secondary Outcome Measure Information:

Title

Incidence of treatment-emergent adverse events (i.e. safety and tolerability of HA)

Description

Summary of adverse events as measured by CTCAE v4.0

Time Frame

30 weeks

Title

Difference in mean joint symptoms between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Difference in mean joint function between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Difference in mean quality of sleep between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Difference in global change between HA and placebo groups

Description

As measured by Patient's Global Impression of Change scale (PGIC) scores

Time Frame

6, 14, and 26 weeks

Title

Difference in mean change in WOMAC subscale 1 scores between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Difference in mean change in WOMAC subscale 2 scores between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Difference in mean change in WOMAC subscale 3 scores between HA and placebo groups

Description

Time Frame

6, 14, and 26 weeks

Title

Time to discontinuation of second aromatase inhibitor due to AIMSS between HA and placebo groups

Description

As measured by patient self-report of mediation compliance (medication diary) and chart review

Time Frame

26 weeks

Title

Proportion of patients that remain on second aromatase inhibitor between HA and placebo groups

Description

As measured by patient self-report of mediation compliance (medication diary) and chart review

Time Frame

26 weeks

Title

Rate of 90% compliance between HA and placebo groups

Description

As measured by patient self-report of mediation compliance (medication diary)

Time Frame

26 weeks

Title

Mean frequency of as needed analgesia between HA and placebo groups

Description

As measured by patient self-report of mediation compliance (medication diary)

Time Frame

6, 14, and 26 weeks

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Study Population ER/PR-Positive Breast Cancer Subjects whose AIMSS resolved with cessation of their AI and are candidates for switching to a different AI and who meet the inclusion and exclusion criteria will be eligible for participation in this study. Inclusion Criteria Age ≥ 18 years old. Had been taking anastrazole or letrozole, and discontinued it within the past 90 days due to pain and/or stiffness. The AI-related pain/stiffness must have resolved. Prior tamoxifen use is allowed. A prior switch from exemestane is allowed. Women who have undergone a total mastectomy or breast conserving surgery for Stage 0-3 breast cancer +/- chemotherapy, +/- antiHer2Neu therapy, +/- radiotherapy. Must have ER and/or PR positive tumors. Women who are postmenopausal by the presence of natural amenorrhea ≥ 12 months or by ovarian ablation (bilateral oophorectomy, radiation, or administration of a gonadotropin-releasing hormone agonist). Eastern Cooperative Oncology Group Performance Score (ECOG PS) 0-3 (Appendix II). Patients may or may not be taking non-opioid analgesics. Adequate renal and hepatic function: i) Include only subjects with AST and ALT < 2.0 × ULN; AP < 1.5 × ULN; total bilirubin < 1.2 × ULN ii) Include only subjects with as calculated creatinine clearance (CrCl) > 60 mL/min determined by the central laboratory using the modified Cockcroft-Gault equation; blood urea nitrogen (BUN) < 1.5 × upper limit of normal (ULN) Written informed consent from subject and ability for subject to comply with the requirements of the study. Exclusion Criteria Presence of residual or recurrent cancer. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. Consumption of HA-containing supplements in the four weeks prior to study. Known allergy to microcrystalline cellulose or HA. Any questionable reaction to injected HA will be thoroughly investigated. Prolonged systemic corticosteroid treatment, except for topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops or local insertion (i.e., intra-articular). A short duration of systemic corticosteroids is allowed but not within 30 days prior to registration. Self-reported compliance issues and lack of regular prescription filling. Previous diagnosis of fibromyalgia and/or rheumatoid arthritis.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Erin Newton, MD

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University Health North Hospital

City

Carmel

State/Province

Indiana

ZIP/Postal Code

46032

Country

United States

Facility Name

Indiana University Health Hospital

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Indiana University Health Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Spring Mill Medical Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46290

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35005781

Citation

Roberts KE, Adsett IT, Rickett K, Conroy SM, Chatfield MD, Woodward NE. Systemic therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer. Cochrane Database Syst Rev. 2022 Jan 10;1(1):CD013167. doi: 10.1002/14651858.CD013167.pub2.

Results Reference

derived

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Trial of Oral Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias

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