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

• ClinicalTrials.gov Identifier: NCT06028022
• Recruitment Status: Recruiting
• First Posted: September 7, 2023
• Last Update Posted: January 12, 2024
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Mayo Clinic

Tracking Information

• First Submitted Date: August 31, 2023
• First Posted Date: September 7, 2023
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: October 18, 2023
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2023)

Change in fatigue scores [ Time Frame: Baseline 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 31, 2023)

• Change in quality of life [ Time Frame: Baseline 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.
• Change in arthralgias [ Time Frame: Baseline 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.
• Incidence of adverse events [ Time Frame: Up 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Condition: Estrogen Receptor-Positive Breast Carcinoma

Intervention

• Dietary Supplement: Mushroom
  Given Reishi mushroom extract PO
  Other Name: CULTIVATED MUSHROOM
• Drug: Placebo Administration
  Given PO
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies

Study Arms

• 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.
  Interventions:

  • Dietary Supplement: Mushroom
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
• 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.
  Interventions:

  • Dietary Supplement: Mushroom
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 31, 2023): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2025
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥ 18 years
• History of breast cancer, estrogen receptor positive (ER+), Her 2 positive or negative
• Fatigue ≥ 4/10
• Currently 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)
• 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 of childbearing potential only
• Provide written 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 CDK4/6 inhibitors or olaparib

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

  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Referral Office; 855-776-0015; mayocliniccancerstudies@mayo.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06028022
• Other Study ID Numbers: MC221002; NCI-2023-06578 ( Registry Identifier: CTRP (Clinical Trials Reporting Program) ); MC221002 ( Other Identifier: Mayo Clinic in Rochester ); 23-005266 ( Other Identifier: Mayo Clinic Institutional Review Board )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stacy D D'Andre, M.D.; Mayo Clinic in Rochester

• PRS Account: Mayo Clinic
• Verification Date: January 2024