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

NCT03384095 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IUSCC-0533
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

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.

Conditions

Breast Neoplasm Female; Arthralgia

Keywords

Aromatase Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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.

  14 weeks

Secondary Outcomes (12)

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

  30 weeks

• Difference in mean joint symptoms between HA and placebo groups

  6, 14, and 26 weeks

• Difference in mean joint function between HA and placebo groups

  6, 14, and 26 weeks

• Difference in mean quality of sleep between HA and placebo groups

  6, 14, and 26 weeks

• Difference in global change between HA and placebo groups

  6, 14, and 26 weeks

Study Arms (2)

Hyaluronic Acid

EXPERIMENTAL

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.

Drug: Hyaluronic Acid (HA)

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Hyaluronic Acid (HA) DRUG

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

Hyaluronic Acid

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Erin Newton: lead
• Indiana University: collaborator
• NOW Foods: collaborator

Study Sites (4)

Indiana University Health North Hospital

Carmel, Indiana, 46032, United States

Location

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Spring Mill Medical Center

Indianapolis, Indiana, 46290, United States

Location

Related Publications (1)

• 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.

  PMID: 35005781 DERIVED

MeSH Terms

Conditions

Arthralgia

Interventions

Hyaluronic Acid

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Erin Newton, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 27, 2017
• Study Start: December 14, 2018
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: January 2, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)