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

Phase 2
Recruiting
Conditions
Estrogen Receptor-Positive Breast Carcinoma
Interventions
Dietary Supplement: Mushroom Extract
Drug: Placebo Administration
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Registration Number
NCT06028022
Lead Sponsor
Mayo Clinic
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
80
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
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Arm I (Reishi mushroom extract, placebo)Questionnaire AdministrationPatients 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.
Arm I (Reishi mushroom extract, placebo)Mushroom ExtractPatients 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.
Arm I (Reishi mushroom extract, placebo)Quality-of-Life AssessmentPatients 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.
Arm II (placebo, Reishi mushroom extract)Quality-of-Life AssessmentPatients 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.
Arm II (placebo, Reishi mushroom extract)Questionnaire AdministrationPatients 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.
Arm I (Reishi mushroom extract, placebo)Placebo AdministrationPatients 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.
Arm II (placebo, Reishi mushroom extract)Placebo AdministrationPatients 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.
Arm II (placebo, Reishi mushroom extract)Mushroom ExtractPatients 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.
Primary Outcome Measures
NameTimeMethod
Change in fatigue scoresBaseline to end of four weeks

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.

Secondary Outcome Measures
NameTimeMethod
Change in quality of lifeBaseline to the end of four weeks and four weeks after cross-over

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.

Incidence of adverse eventsUp to 30 days follow-up

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.

Change in arthralgiasBaseline to the end of four weeks and four weeks after cross-over

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.

Trial Locations

Locations (20)

MMCORC CentraCare Monticello Cancer Center

🇺🇸

Monticello, Minnesota, United States

Sanford Worthington Medical Center

🇺🇸

Worthington, Minnesota, United States

Mayo Clinic Health System in Albert Lea

🇺🇸

Albert Lea, Minnesota, United States

Essentia Health Baxter Clinic

🇺🇸

Baxter, Minnesota, United States

Sanford Joe Lueken Cancer Center

🇺🇸

Bemidji, Minnesota, United States

Essentia Health Saint Joseph's Medical Center

🇺🇸

Brainerd, Minnesota, United States

Essentia Health Deer River Clinic

🇺🇸

Deer River, Minnesota, United States

Essentia Health Saint Mary's - Detroit Lakes Clinic

🇺🇸

Detroit Lakes, Minnesota, United States

Essentia Health Cancer Center

🇺🇸

Duluth, Minnesota, United States

Essentia Health Ely Clinic

🇺🇸

Ely, Minnesota, United States

Essentia Health Hibbing Clinic

🇺🇸

Hibbing, Minnesota, United States

Essentia Health Fosston

🇺🇸

Fosston, Minnesota, United States

Sanford Thief River Falls Medical Center

🇺🇸

Thief River Falls, Minnesota, United States

Essentia Health Virginia Clinic

🇺🇸

Virginia, Minnesota, United States

Essentia Health International Falls Clinic

🇺🇸

International Falls, Minnesota, United States

Mayo Clinic Health Systems-Mankato

🇺🇸

Mankato, Minnesota, United States

Essentia Health Moose Lake

🇺🇸

Moose Lake, Minnesota, United States

Essentia Health Park Rapids

🇺🇸

Park Rapids, Minnesota, United States

Mayo Clinic in Rochester

🇺🇸

Rochester, Minnesota, United States

Essentia Health Sandstone

🇺🇸

Sandstone, Minnesota, United States

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