Reishi Mushroom Extract for Fatigue and/or Arthralgias/Myalgias in Patients With Breast Cancer on Aromatase Inhibitors

Reishi Mushroom Extract for Fatigue and/or Arthralgias in Patients With Breast Cancer on Aromatase Inhibitors: A Randomized Phase II MNCCTN Trial

This phase II trial tests how well Reishi mushroom extract works in treating fatigue and/or joint/muscle pain (arthralgias/myalgias) in patients with breast cancer on aromatase inhibitors. Fatigue and arthralgias/myalgias are common symptoms in breast cancer patients taking aromatase inhibitors (AI). Given the long duration of AI treatment for some women (up to 10 years), these symptoms can significantly impact quality of life and premature discontinuation of AIs, a beneficial medication. Reishi mushrooms are among several medicinal mushrooms that have been used for hundreds of years, mainly in Asian countries, to help enhance the immune system, reduce stress, improve sleep, and lessen fatigue. Reishi mushroom extracts have not been studied explicitly for treatment-induced arthralgias/myalgias, but have been shown to improve quality of life, muscular strength, pain, and flexibility. Information from this study may help researchers determine the effect of Reishi mushroom extract on fatigue and arthralgias/myalgias in breast cancer patients receiving an AI.

Study Overview

• Status: Recruiting
• Conditions: Estrogen Receptor-Positive Breast Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Placebo Administration; Dietary supplement: Mushroom Extract

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of 1,000 mg three times daily (TID) of Reishi mushroom extracts as therapy for cancer-related fatigue measured by uniscale measurement at the end of four weeks.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of Reishi mushroom extracts as therapy for cancer-related arthralgias at the end of four weeks and four weeks after cross-over as measured by the Brief Pain index (BPI)-adapted for AI associated arthralgias.

II. To evaluate the effect of Reishi mushroom extracts on cancer-related quality of life (QOL), as measured by uniscale, at the end of four weeks and four weeks after cross-over.

III. To evaluate the efficacy of Reishi mushroom extracts on mood, as assessed by the World Health Organization Five Well-Being Index (WHO-5) item well-being scale, at the end of four weeks and four weeks after cross-over.

IV. To evaluate treatment toxicity between the two treatment arms, as measured by a patient symptom experience diary and weekly calls from the study team.

V. To evaluate the interest, knowledge, and acceptance of integrative treatments for cancer-related symptoms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive Reishi mushroom extract orally (PO) TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Minnesota
    • Albert Lea, Minnesota, United States, 56007
      • Active, not recruiting
      • Mayo Clinic Health System in Albert Lea
    • Baxter, Minnesota, United States, 56425
      • Active, not recruiting
      • Essentia Health Baxter Clinic
    • Bemidji, Minnesota, United States, 56601
      • Active, not recruiting
      • Sanford Joe Lueken Cancer Center
    • Brainerd, Minnesota, United States, 56401
      • Active, not recruiting
      • Essentia Health Saint Joseph's Medical Center
    • Deer River, Minnesota, United States, 56636
      • Active, not recruiting
      • Essentia Health Deer River Clinic
    • Detroit Lakes, Minnesota, United States, 56501
      • Active, not recruiting
      • Essentia Health Saint Mary's - Detroit Lakes Clinic
    • Duluth, Minnesota, United States, 55805
      • Active, not recruiting
      • Essentia Health Cancer Center
    • Ely, Minnesota, United States, 55731
      • Active, not recruiting
      • Essentia Health Ely Clinic
    • Fosston, Minnesota, United States, 56542
      • Active, not recruiting
      • Essentia Health Fosston
    • Grand Rapids, Minnesota, United States, 55744
      • Active, not recruiting
      • Fairview Grand Itasca Clinic & Hospital
    • Hibbing, Minnesota, United States, 55746
      • Active, not recruiting
      • Essentia Health Hibbing Clinic
    • Hibbing, Minnesota, United States, 55746
      • Active, not recruiting
      • Fairview Range Medical Center
    • International Falls, Minnesota, United States, 56649
      • Active, not recruiting
      • Essentia Health International Falls Clinic
    • Mankato, Minnesota, United States, 56001
      • Active, not recruiting
      • Mayo Clinic Health Systems-Mankato
    • Monticello, Minnesota, United States, 55362
      • Withdrawn
      • MMCORC CentraCare Monticello Cancer Center
    • Moose Lake, Minnesota, United States, 55767
      • Active, not recruiting
      • Essentia Health Moose Lake
    • Park Rapids, Minnesota, United States, 56470
      • Active, not recruiting
      • Essentia Health Park Rapids
    • Princeton, Minnesota, United States, 55731
      • Active, not recruiting
      • Fairview Northland Medical Center
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Stacy D. D'Andre, M.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
    • Sandstone, Minnesota, United States, 55072
      • Active, not recruiting
      • Essentia Health Sandstone
    • Thief River Falls, Minnesota, United States, 56701
      • Active, not recruiting
      • Sanford Thief River Falls Medical Center
    • Virginia, Minnesota, United States, 55792
      • Active, not recruiting
      • Essentia Health Virginia Clinic
    • Worthington, Minnesota, United States, 56187
      • Active, not recruiting
      • Sanford Worthington Medical Center

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:

• Age ≥ 18 years
• History of breast cancer, estrogen receptor positive (ER+), Her 2 positive or negative
• Fatigue ≥ 4/10
• Currently post-menopausal (as defined by National Comprehensive Cancer Network (version 4.2024), taking any aromatase inhibitor in the curative setting and planning to be on such for at least 8 weeks after registration. [Patients on concurrent ovarian suppression (such as with leuprolide acetate, goserelin) are allowed]; CDK 4/6 inhibitors abemaciclib, ribociclib ARE allowed
• Prior treatment: last chemotherapy ≥ 90 days prior to randomization (if treated with chemotherapy)
• On a stable dose of pain medications if pain medications are being regularly used. (i.e., no change in dosage in the past 30 days)
• If on supplements, must be on stable dose with no plan to change; not on or planning any acupuncture or other specific supportive modalities for fatigue or AI arthralgias
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• White blood cell count (WBC) ≥ 3,000/mm^3 (obtained ≤ 30 days prior to randomization)
• Hemoglobin ≥ 10 g/dL (obtained ≤ 30 days prior to randomization)
• Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to randomization)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 30 days prior to randomization)
• Alanine aminotransferase (ALT) or aspartate transaminase (AST) ≤ 1.2 x ULN (obtained ≤ 30 days prior to randomization)
• Prothrombin time (PT)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (obtained ≤ 30 days prior to randomization)
• Negative pregnancy test done ≤ 7 days prior to registration, for persons on concurrent ovarian suppression only
• Provide informed consent
• Ability to complete questionnaires
• Willing to return to enrolling institution during the active monitoring phase of the study
• Patients who have had a recent surgery or procedure should be healed and cleared by their clinician and/or surgeon per local standards, prior to registration

Exclusion Criteria:

• Other known uncontrolled medical conditions causing fatigue such as untreated thyroid disease, depression, fibromyalgia, chronic fatigue syndrome, infection, autoimmune disease, or active/untreated hepatitis

• Allergy to mushrooms

• On anticoagulation medication or aspirin or having a known bleeding disorder

• On any specific medication for fatigue (e.g., methylphenidate)

• Metastatic cancer diagnosis (history of nodal metastases is allowed)

• Chronic steroid use, unless on physiologic replacement doses

• Current use of any medical mushrooms

• On medications for diabetes

• History of symptomatic hypotension

• Taking CYP3A4, CYP2D6 sensitive substrates which can be located at the following link: https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems

• Drugs which exhibit either >20% inhibition or >20% induction of CYP2E1 in vivo, such as: Acetaminophen, Dapsone, Enflurane, Halothane, Isoflurane, & Theophylline

• Taking olaparib

• Any of the following because this study involves an agent that has unknown genotoxic, mutagenic and teratogenic effects:

  • Pregnant persons
  • Nursing persons
  • Persons on concurrent ovarian suppression who are unwilling to employ adequate contraception (e.g., hormonal methods, barrier methods, intrauterine device, abstinence)

• Planned surgery or procedure during time on study and ≤ 14 days after last dose, due to bleeding risks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Reishi mushroom extract, placebo); Patients receive Reishi mushroom extract PO TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO; Dietary supplement: Mushroom Extract; Given Reishi mushroom extract PO; Other Names: Agaricus bisporus Extract; Cultivated Mushroom
Experimental: Arm II (placebo, Reishi mushroom extract); Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Drug: Placebo Administration; Given PO; Dietary supplement: Mushroom Extract; Given Reishi mushroom extract PO; Other Names: Agaricus bisporus Extract; Cultivated Mushroom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fatigue scores	Based on a single item fatigue uniscale question. Will be compared between arms using a two-sided two-sample t-test assuming equal variances in each group.	Baseline to end of four weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life	Measured by the World Health Organization-Five Well-Being Index. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach.	Baseline to the end of four weeks and four weeks after cross-over
Change in arthralgias	Measured by the Brief Pain Inventory for Aromatase Inhibitor Induced Arthralgia. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach.	Baseline to the end of four weeks and four weeks after cross-over
Incidence of adverse events	Measured by the symptom experience diary. Will be compared between arms using two-sample, two-sided t-tests assuming equal variances and alpha levels of 5%. The analyses of the crossover portion of the study will be descriptive. Mean values will be plotted over time by arm. A formal crossover analysis will also be performed using Senn's linear modeling approach.	Up to 30 days follow-up

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Stacy D. D'Andre, MD, Mayo Clinic in Rochester

Publications and helpful links

Helpful Links

• <p>Mayo Clinic Clinical Trials</p>

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2023
• Primary Completion (Estimated): May 15, 2029
• Study Completion (Estimated): June 15, 2029

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 4, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: MC221002; MC221002 (Other Identifier: Mayo Clinic in Rochester); NCI-2023-06578 (Registry Identifier: CTRP (Clinical Trials Reporting Program)); 23-005266 (Other Identifier: Mayo Clinic Institutional Review Board); MNCCTN032 (Other Identifier: Minnesota Cancer Clinical Trials Network)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No