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WithdrawnNCT03384095Updated Jan 2, 2019

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

A Phase 2 interventional study of Hyaluronic Acid (HA) and Placebo in Breast Neoplasm Female and Arthralgia, sponsored by Erin Newton. Withdrawn at 4 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-01-02.

Sponsored by Erin Newton · Phase 2, Interventional, and Supportive care

Why this study was withdrawn
study abandoned prior to opening to accrual or study start
Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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.

Read the detailed description

Primary Objective To determine whether oral HA will prevent AI-induced arthralgias and preserve physical function.

Secondary Objectives

  1. To explore whether oral HA will have an acceptable safety and tolerability profile.
  2. To determine whether oral HA will prevent other AI associated symptoms as assessed by patient reported outcomes (PRO's).
  3. 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.

02

Conditions studied

  • Breast Neoplasm Female
  • Arthralgia

Keywords

  • Aromatase Inhibitors
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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

Inclusion Criteria

  1. Age ≥ 18 years old.
  2. 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.
  3. Prior tamoxifen use is allowed.
  4. A prior switch from exemestane is allowed.
  5. Women who have undergone a total mastectomy or breast conserving surgery for Stage 0-3 breast cancer +/- chemotherapy, +/- antiHer2Neu therapy, +/- radiotherapy.
  6. Must have ER and/or PR positive tumors.
  7. 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).
  8. Eastern Cooperative Oncology Group Performance Score (ECOG PS) 0-3 (Appendix II).
  9. Patients may or may not be taking non-opioid analgesics.
  10. 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)

  11. Written informed consent from subject and ability for subject to comply with the requirements of the study.

Exclusion criteria

Exclusion Criteria

  1. Presence of residual or recurrent cancer.
  2. 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.
  3. Consumption of HA-containing supplements in the four weeks prior to study.
  4. Known allergy to microcrystalline cellulose or HA. Any questionable reaction to injected HA will be thoroughly investigated.
  5. 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.
  6. Self-reported compliance issues and lack of regular prescription filling.
  7. Previous diagnosis of fibromyalgia and/or rheumatoid arthritis.
04

Study design

Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    Hyaluronic Acid

    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 comparator
    Placebo

    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

  • DrugHyaluronic Acid (HA)

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

  • OtherPlacebo

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

05

What researchers measure

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.

    Time frame: 14 weeks

Secondary outcomes

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

    Summary of adverse events as measured by CTCAE v4.0

    Time frame: 30 weeks

  2. 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.

    Time frame: 6, 14, and 26 weeks

  3. 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.

    Time frame: 6, 14, and 26 weeks

  4. 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.

    Time frame: 6, 14, and 26 weeks

  5. Difference in global change between HA and placebo groups

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

    Time frame: 6, 14, and 26 weeks

  6. 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.

    Time frame: 6, 14, and 26 weeks

  7. 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.

    Time frame: 6, 14, and 26 weeks

  8. 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 frame: 6, 14, and 26 weeks

  9. 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

    Time frame: 26 weeks

  10. 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

    Time frame: 26 weeks

  11. Rate of 90% compliance between HA and placebo groups

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

    Time frame: 26 weeks

  12. Mean frequency of as needed analgesia between HA and placebo groups

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

    Time frame: 6, 14, and 26 weeks

06

Study locations

4 sites
  • Indiana University Health North Hospital
    Carmel, Indiana 46032, United States
  • Indiana University Health Hospital
    Indianapolis, Indiana 46202, United States
  • Indiana University Health Melvin and Bren Simon Cancer Center
    Indianapolis, Indiana 46202, United States
  • Spring Mill Medical Center
    Indianapolis, Indiana 46290, United States
07

References and documents

Publications

  • 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. PubMed 35005781 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03384095
Lead sponsor
Erin Newton
Collaborators
Indiana University, NOW Foods
Responsible party
Erin Newton (Assistant Professor of Clinical Medicine, Indiana University School of Medicine) — Sponsor-investigator
First posted
Dec 27, 2017
Start date
Dec 14, 2018
Primary completion
Dec 14, 2018
Completion
Dec 14, 2018
Last update
Jan 2, 2019

Study contacts

Erin Newton, MD
principal investigator · Indiana University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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