Breast Neoplasm FemalePhase 2NCT03384095
Trial of Oral Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
A Phase 2 study testing Hyaluronic Acid (HA) in people with Breast Neoplasm Female and Arthralgia, run by Erin Newton at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Female, Arthralgia
- What is being tested?
- Hyaluronic Acid (HA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Dec 2018to 14 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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:
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Indiana University Health North Hospital
Carmel, Indiana, 46032
Indiana University Health Hospital
Indianapolis, Indiana, 46202
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Spring Mill Medical Center
Indianapolis, Indiana, 46290
About this study
Official title: Single Center, Placebo-Controlled Trial of Oral High-Molecular Weight Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
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
- 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.
- Conditions
- Breast Neoplasm Female, Arthralgia
- Being tested
- Hyaluronic Acid (HA), Placebo
- Keywords
- Aromatase Inhibitors
- Medical subject headings
- Arthralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic Acid (HA)Drug
Dosage form: hyaluronic capsules; Dose: 100 mg; Frequency: twice daily; Duration: 26 weeks
PlaceboOther
Dosage form: microcrystalline cellulose (MCC) capsules; Dose: approx. 100 mg (determined by weight of HA counterpart); Frequency: twice daily; Duration: 26 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 weeks
Secondary outcomes (12)
Incidence of treatment-emergent adverse events (i.e. safety and tolerability of HA)
Summary of adverse events as measured by CTCAE v4.0
Measured: 30 weeks
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.
Measured: 6, 14, and 26 weeks
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.
Measured: 6, 14, and 26 weeks
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.
Measured: 6, 14, and 26 weeks
Difference in global change between HA and placebo groups
As measured by Patient's Global Impression of Change scale (PGIC) scores
Measured: 6, 14, and 26 weeks
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.
Measured: 6, 14, and 26 weeks
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.
Measured: 6, 14, and 26 weeks
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.
Measured: 6, 14, and 26 weeks
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
Measured: 26 weeks
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
Measured: 26 weeks
Rate of 90% compliance between HA and placebo groups
As measured by patient self-report of mediation compliance (medication diary)
Measured: 26 weeks
Mean frequency of as needed analgesia between HA and placebo groups
As measured by patient self-report of mediation compliance (medication diary)
Measured: 6, 14, and 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2017
- Study start14 Dec 2018
- Primary completion14 Dec 2018
- Study completion14 Dec 2018
Why it stopped: study abandoned prior to opening to accrual or study start
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast Neoplasm FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erin Newton
- Sponsor type
- University, hospital or other
- Collaborators
- Indiana University, NOW Foods
- Responsible party
- Sponsor-investigator, Erin Newton, Indiana University
- Investigators
- Erin Newton, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03384095
- Sponsor's protocol ID
- IUSCC-0533
- Status last verified
- Dec 2018
- First submitted
- 18 Dec 2017
- Last updated
- 2 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Center, Placebo-Controlled Trial of Oral High-Molecular Weight Hyaluronic Acid for the Prevention of Aromatase Inhibitor-Associated Arthralgias
- ClinicalTrials.gov ID
- NCT03384095
- Acronym / sponsor ID
- IUSCC-0533
- Conditions
- Breast Neoplasm Female, Arthralgia
- Keywords
- Aromatase Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: study abandoned prior to opening to accrual or study start
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Erin NewtonUniversity, hospital or other
- Collaborators
- Indiana University, NOW Foods
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 14 Dec 2018 (actual)
- First posted
- 27 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hyaluronic Acid | Experimental | Drug: Hyaluronic Acid (HA)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. |
| Placebo | Placebo comparator | Other: PlaceboSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyaluronic Acid (HA)Dosage form: hyaluronic capsules; Dose: 100 mg; Frequency: twice daily; Duration: 26 weeks | Drug | Hyaluronic Acid |
| PlaceboDosage form: microcrystalline cellulose (MCC) capsules; Dose: approx. 100 mg (determined by weight of HA counterpart); Frequency: twice daily; Duration: 26 weeks | Other | Placebo |
Primary outcome
Difference in mean change in joint pain between HA and placebo groups
Time frame: 14 weeks
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.
12 secondary outcomes
Incidence of treatment-emergent adverse events (i.e. safety and tolerability of HA)
Time frame: 30 weeks
Difference in mean joint symptoms between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in mean joint function between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in mean quality of sleep between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in global change between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in mean change in WOMAC subscale 1 scores between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in mean change in WOMAC subscale 2 scores between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Difference in mean change in WOMAC subscale 3 scores between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Time to discontinuation of second aromatase inhibitor due to AIMSS between HA and placebo groups
Time frame: 26 weeks
Proportion of patients that remain on second aromatase inhibitor between HA and placebo groups
Time frame: 26 weeks
Rate of 90% compliance between HA and placebo groups
Time frame: 26 weeks
Mean frequency of as needed analgesia between HA and placebo groups
Time frame: 6, 14, and 26 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2019.
- Derived from this study: PubMed 35005781Roberts 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erin Newton, MD principal investigator
Indiana University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyaluronic Acid (HA) in people with Breast Neoplasm Female and Arthralgia, run by Erin Newton at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in mean change in joint pain between HA and placebo groups (time frame: 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03384095, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2019.