Opera® for Aromatase Inhibitor-related Arthralgia Management (AIA) (AIA)

Use of an Alfa-lipoic, Methylsulfonylmethane and Bromelain Dietary Supplement (Opera®) for Aromatase Inhibitor-related Arthralgia Management (AIA)

In this phase II, multicenter, self-controlled clinical trial, we will evaluate the safety and efficacy of OPERA® for treating anti-aromate inhibitors (AIs) induced arthralgia. The diagnosis of arthralgia will be based on the NCI-CTCAE v4.0 grade of ≥ 1 , A disorder characterized by a sensation of marked discomfort in a joint, mild pain (grade 1). Arthralgia will be assessed at the enrollment and every two months until the sixth month.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Arthralgia; Hormone Receptor Positive Tumor
• Intervention / Treatment: Dietary supplement: OPERA

Detailed Description

Aromatase Inhibitors (AIs) are recommended for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. Compared with Tamoxifen, third generation aromatase inhibitors have been shown to significantly improve disease free survival (DFS), and include the steroidal inhibitor exemestane, and the nonsteroidal inhibitors, anastrozole and letrozole. Although the AIs are associated with fewer thromboembolic events and endometrial abnormalities than is tamoxifen, approximately 25% of postmenopausal women on AI report arthralgia, skeletal, and muscle pain. The multicentre double-blind placebo-controlled ma.17 trial by the National Cancer Institute of Canada Clinical Trials Group revealed marked increases in arthralgia (25% vs. 21%) and myalgia (15% vs. 12%) in patients on letrozole as compared with those on placebo. The Intergroup Exemestane Study shown a link between arthralgia and the ai exemestane (5.4% exemestane vs. 3.6% tamoxifen).The Arimidex, Tamoxifen Alone or in Combination (atac) trial, after 68 months' median follow-up, showed that the incidence of arthralgia was significantly higher in the anastrozole group than in the tamoxifen group [1100 of 3092 (35.6%) vs. 911 of 3094 (29.4%) patients]. Currently, evidences of drugs efficacy to reduce these side effects are sparse.OPERA® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-Lipoic acid (240mg), BS (40mg), MSM (200mg) and Bromelain (20mg) are combined together in a single hard-gelatin capsule. The aim of this prospective study is to determine the efficacy and safety of OPERA® supplementation in a series of patients affected by arthralgia during AI treatment.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Florence, Italy, 50100
    • Azienda Ospedaliero Universitaria Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 18 years or older
• Karnofsky performance score≥70
• Indication for AI treatment in adjuvant setting for breast cancer
• Arthralgia with grade ≥0-1

Exclusion Criteria:

• Concomitant diseases, e.g. diabetes, renal insufficiency, alcohol abuse
• Concomitant rheumatological disease (Rheumatoid arthritis, Spondyloarthropathies, Psoriatic arthritis, etc.)
• Concomitant endocrinological disease (Acromegaly , Emocromatosis, etc)
• Any conditions that would complicate arthralgia assessment (e.g. Trauma, Glucocorticoid withdrawal, Hypertrophic osteoarthropathy, Osteoarthritis, Avascular necrosis, Gout, Systemic lupus erythematosus, Septic arthritis, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPERA; Women receiving adjuvant aromates-inhibitor with arhtralgia grade ≥ 1 (CTACAE 4.03)	Dietary supplement: OPERA; All patients were required to take an OPERA® capsule (dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule) once daily,from enrollment up to sixth months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of AI induced arthralgia at 6 months	Reduction of AI-induced arthralgia assessed with VAS scale (0, no pain, to 5, worst pain)	6 months
Reduction of AI induced arthralgia at 6 months	Reduction of AI-induced arthralgia assessed with PRAI questionnaire (16 items that query pain severity over the last 7 days in eight joints using a rating scale of 0-10, with 10 being greatest severity)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QoL	Quality of life assessed with FACT-ES questionnaire (19 items which assess endocrine complaints and adverse effects with response scores ranging from 0 to 4 ('not at all', 'a little bit', 'somewhat', 'quite a bit', and 'very much.')	6 months
Compliance	Compliance to AI therapy (percentage of patients that have not discontinued and/or changed originally prescribed anti-aromatase inhibitor)	6 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Investigators: Principal Investigator: Isacco Desideri, MD, Radiation Oncology Unit, AOU Careggi; Study Chair: Lorenzo Livi, MD, Radiation Oncology Unit, AOU Careggi

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: November 8, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (Actual): November 13, 2019

Study Record Updates

• Last Update Posted (Actual): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 11, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: breast cancer; dietary supplement; arthralgia; luminal tumor; anti-aromatase inhibitors
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Arthralgia
• Other Study ID Numbers: OPERA2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No