Health-related Quality of Life-intervention in Survivors of Breast and Other Cancers Experiencing Cancer-related Fatigue Using Traditional Chinese Medicine: The HERBAL Trial

Phase 2

• Conditions: Cancer; Fatigue; Cognitive Impairment
• Interventions: Other: Placebo; Other: Modified Xiang Bei Yang Rong Tang

• Registration Number: NCT04104113
• Lead Sponsor: National University of Singapore

Brief Summary

This study is a phase 2, randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of a Traditional Chinese Medicine decoction, the modified Xiang Bei Yang Rong Tang, in alleviating cancer related fatigue in cancer survivors.

Detailed Description

Cancer-related fatigue (CRF) is a distressing, persistent and subjective sense of physical, emotional, or cognitive tiredness related to cancer or its treatment. Currently there is a lack of effective conventional pharmacological intervention for treating this condition. Traditional Chinese Medicine (TCM) could be alternative therapy for managing CRF.

This study is a phase 2, randomized, double-blinded, placebo-controlled trial to examine the efficacy and safety of a TCM decoction, the modified Xiang Bei Yang Rong Tang (XBYRT) in alleviating CRF in cancer survivors. Study participants recruited from National Cancer Centre Singapore (NCCS) will be randomized to receive either the XBYRT or placebo decoction. Participants will take their assigned decoction daily for a duration of 8 weeks and will be assessed using patient reported outcome (PRO) questionnaires. PROs used are the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ 30) for QOL, the Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) for fatigue and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Version 3 for cognitive abilities. The changes in scores measured by these assessment tools will be compared between the XBYRT intervention and placebo groups. Blood biomarkers such as inflammatory cytokines, mitochondrial DNA and oxidative stress markers will also be evaluated in the study participants. Additionally, adverse events or serious adverse events in participants will be monitored for safety.

Results from this study will provide a better understanding on the role of TCM in managing CRF.

Study Timeline

• Study First Submitted: 2019-09-24
• Study First Submitted QC: 2019-09-24
• Study First Posted: 2019-09-26
• Study Start: 2019-10-24
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-13
• Last Update Posted: 2020-06-16
• Primary Completion: 2021-05-30
• Study Completion: 2022-06-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Age ≥21 years
2. Clinically diagnosed cancer (Stages I-III)
3. Completed surgery/chemotherapy/radiotherapy for at least 1 month
4. At least one month after starting on aromatase inhibitors or ovarian suppression for breast cancer survivors
5. Not expected to receive surgery/chemotherapy/radiotherapy next 10 weeks
6. Fatigue screening score ≥4 for past 7 days
7. Life expectancy ≥3 months
8. Patients satisfy TCM syndrome differentiation as qi and blood deficiency Experience 2 major symptoms coupled with typical tongue and pulse conditions; 2 major symptoms and 1 possible symptom coupled with tongue and pulse conditions; 1 major symptom and at least 2 possible symptoms coupled with tongue and pulse conditions
9. Able to read and understand English or Mandarin

Exclusion Criteria

1. Cancer recurrence and/or metastasis
2. Untreated co-morbidities causing fatigue (e.g. Severe anaemia, thyroid disorder)
3. On medications that cause fatigue (e.g. beta blockers)
4. Patients on warfarin
5. Cancer survivors receiving adjuvant therapy during the study period. Aromatase inhibitors and anti-HER2 monoclonal antibodies are acceptable.
6. Receiving or planning to receive treatment from other TCM practitioners during the study period
7. Breast feeding or intending to conceive/get pregnant during the study treatment period
8. Patients who present with yin deficiency and deficiency syndromes (e.g. phlegm-dampness, blood stasis, toxic-heat and qi stagnation)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants assigned to receive placebo (contains 5% of XBYRT) granules
XBYRT decoction	Modified Xiang Bei Yang Rong Tang	Participants assigned to receive the modifed Xiang Bei Yang Rong Tang granules

Primary Outcome Measures

Name	Time	Method
Difference in Global Health Status (GHS) score	8 weeks from baseline	Difference in Global Health Status (GHS) score from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) between XBYRT interventional and placebo arms from baseline to 8 weeks after baseline. The GHS scale ranges in score from 0-100. A higher score represents a better quality of life

Secondary Outcome Measures

Name	Time	Method
Difference in Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) version 3 scores	4, 8 and 10 weeks from baseline	Difference in FACT-Cog V3 scores between XBYRT interventional and placebo arms. FACT-Cog v.3 will be used to assess subjective cognitive disturbances. These disturbances are assessed via 33 items in the domains of concentration, functional interference, mental acuity, memory, multitasking and verbal fluency (total score ranges from 0-148). A lower score represents worse cognitive function.
Incidence of adverse events	baseline, and 4, 8 and 10 weeks from baseline	Adverse events reported according to the Adverse events Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Oxidative stress markers : malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)	baseline, 4, 8 and 10 weeks from baseline	Plasma oxidative stress markers levels in XBYRT interventional and placebo arms
Difference in EORTC QLQ-C30 version 3.0 Functional and Symptom scale scores	4, 8 and 10 weeks from baseline	Difference in EORTC QLQ-C30 scores between XBYRT interventional and placebo arms. The EORTC QLQ-C30 consists of 30 items across functional domains, symptoms domains and a global health status domain. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high level of functioning. A high score for a symptom scale represents a high level of problems.
Difference in Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) scores	4, 8 and 10 weeks from baseline	Difference in MFSI-SF scores between XBYRT interventional and placebo arms. THE MFSI-SF consists of 30 items and has 5 subscales, each with 6 items: general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigour. The MFSI-SF measures different dimensions of fatigue, which can be combined to obtain an overall score. A higher score represents worse fatigue (total score ranges from -24 to 96)
Mitochondrial DNA (mtDNA) content	baseline, 4, 8 and 10 weeks from baseline	Mitochondrial DNA (mtDNA) content reduction in XBYRT interventional and placebo arms
Inflammatory cytokines : C reactive protein (CRP) and cytokines TNF-α, IL-1β, IL-6, and IL-8	baseline, 4, 8 and 10 weeks from baseline	Plasma inflammatory cytokine levels in XBYRT interventional and placebo arms

Trial Locations

Locations (1)

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore