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Trial registered on ANZCTR


Registration number
ACTRN12619000368134p
Ethics application status
Submitted, not yet approved
Date submitted
4/03/2019
Date registered
8/03/2019
Date last updated
8/03/2019
Date data sharing statement initially provided
8/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title

Evaluating the effectiveness and safety of a ginger supplement for chemotherapy-induced nausea and vomiting in a New Zealand population.
Scientific title
Supplemental Prophylactic Intervention for Chemotherapy induced nausea and Emesis (SPICE-NZ) trial of the efficacy and safety of adjuvant ginger supplementation: A New Zealand randomized controlled feasibility trial.
Secondary ID [1] 296341 0
Nil Known
Universal Trial Number (UTN)
U1111-1222-3745
Trial acronym
SPICE-NZ
Linked study record
This record is a sub-study of ACTRN12616000416493

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy Induced Nausea 310077 0
Chemotherapy induced Emesis 311878 0
Condition category
Condition code
Cancer 308827 308827 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1.2g standardised non-synthetic Ginger (Zingiber officinale) extract in capsule form; over-encapsulated with a non-gelatin capsule for blinding. Frequency: 4x300mg capsules (1.2g total) per day, every 3-5 hours with food. The ginger is standardised to contain 5% gingerols (15mg active ingredient per capsule; 60mg gingerols in total). Duration: 5 days per chemotherapy cycle (Day of chemotherapy and 4 days directly after) for three 3 cycles. Initial dose is 1 hour before chemotherapy commences. All participants will be provided the supplement or placebo in identical glass bottles of 60 capsules with a single desiccant for use throughout the entire treatment period. The usual diet is unmodified, although participants will be advised to consume no fresh ginger or ginger-containing products. Strategies to monitor adherance include the collection of supplement containers with all unused supplements after T3 of the third and final chemotherapy cycle and subjects will be given a mobile phone with a pre-installed application to log events in electronic diaries.
Intervention code [1] 312683 0
Treatment: Drugs
Comparator / control treatment
The placebo capsules given to the control group contain 150 - 200mg of the inner filler microcrystalline cellulose in a non-gelatin capsule, and will be prescribed the same dosing regimen as the intervention group.
Control group
Placebo

Outcomes
Primary outcome [1] 308418 0
Nausea-related impact on quality of life.
1. Instrument: Functional Living Index – Emesis – 5 Day Recall (FLIE-5DR)
Measure: Cronbach’s a > 0.79
2. . Electrogastrography (EGG) data. High-resolution EGG will be used as an objective measure of subjectively-reported patient nausea, and to correlate the onset nausea with disordered gastric electrical activity.
Timepoint [1] 308418 0
(1) Outcomes will be at baseline (T0); >5 days prior to chemotherapy), 1 day prior to chemotherapy (T1), on the day of chemotherapy (T2), and 4-days post-chemotherapy (T3), and 5-8 days post chemotherapy (T4 - primary timepoint) for three chemotherapy cycles
Secondary outcome [1] 354907 0
Acute and delayed nausea, vomiting occurrence, duration, and frequency
Instrument: Multinational Association of Supportive in Cancer Anti-emesis (MAT) tool
Measure: Spearman’s r=0.87; Cronbach’s a >0.77
Timepoint [1] 354907 0
Outcomes will be at baseline (T0); >5 days prior to chemotherapy), 1 day prior to chemotherapy (T1), on the day of chemotherapy (T2), and 4-days post-chemotherapy (T3), and 5-8 days post chemotherapy (T4 - primary timepoint) for three chemotherapy cycles
Secondary outcome [2] 354908 0
Fatigue
Instrument: Functional Assessment of Chronic Illness Therapy (FACIT) – Fatigue Scale
Timepoint [2] 354908 0
Outcomes will be at baseline (T0); >5 days prior to chemotherapy), 1 day prior to chemotherapy (T1), on the day of chemotherapy (T2), and 4-days post-chemotherapy (T3), and 5-8 days post chemotherapy (T4 - primary timepoint) for three chemotherapy cycles
Secondary outcome [3] 354909 0
Nutrition status
Instrument: Scored Patient-Generated Subjective Global Assessment (PG-SGA)
Timepoint [3] 354909 0
At the commencement of first three chemotherapy cycles
Secondary outcome [4] 354910 0
Global quality of life
Instrument: EQ-5D-5L
Timepoint [4] 354910 0
Day before chemotherapy and Day-5 of the first three chemotherapy cycles
Secondary outcome [5] 354911 0
Anxiety and depression (predictive factor for CIN)
Instrument: Hospital Depression and Anxiety Scale (HADS)
Measure: Cronbach’s a >0.82
Timepoint [5] 354911 0
Day 1 of the first three chemotherapy cycles

Eligibility
Key inclusion criteria
• Chemotherapy-naive (i.e. have not yet started chemotherapy) patients scheduled for chemotherapy classed as moderately or severely emetogenic
• Aged >18 years.
• Adequate physical function: baseline Karnofsky score > 60 (patient interview).
• Females of child-bearing age entering this study must use an appropriate form of contraception. If a patient becomes pregnant during the course of this trial, they must notify the investigator as soon as possible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Patients scheduled for concurrent radiotherapy (medical note observation and/or discussion with treating oncologist).
• Non-English speaking persons
• People with severe cognitive impairment preventing their ability to fully understand the purpose of the study, adhere to the intervention and complete data collection forms. This will include diagnoses such as temporary delirium or dementia; but will be informed by the patients treating oncologist.
• Pregnant or lactating women (medical note observation and confirmed via patent interview).
• Concurrent use of other ginger-containing supplements and ingestion of large quantities of ginger (consumption of >1 ginger product > 4 days in the past week) (patient interview).
• History of adverse reactions to ginger (patient interview).
• Diagnosed with liver disease (medical note observation).
• Experiencing nausea and vomiting for reasons other than chemotherapy (medical note observation and/or discussion with treating oncologist), including:
o Prescribed medications with nausea-related side-effects, e.g. newly-prescribed opioids,
o Diagnosed with malignancies that might cause nausea and vomiting due to the position of the cancer e.g. gastrointestinal cancer,
o Metabolic risk factors for nausea e.g. electrolyte imbalances
o Mechanical risk factors for nausea e.g. intestinal obstruction
• Chronic alcohol use as indicated by >14 standard drinks per week (predictive factor for decreased CIN risk)(29) (medical note observation and confirmed via patient interview).
• Severe thrombocytopenia or likely to experience severe thrombocytopenia (platelets <50 x 10^9/L) (medical note observation).
• Gallstones.
• Currently prescribed warfarin, anti-coagulant therapy, hypoglycaemics, insulin, cyclosporine, tacrolimus, and nonsteroidal anti-inflammatory drugs (hypothesised interactions) (medical note observation).
• Swallowing difficulties preventing supplement ingestion (medical note observation).
• Self-prescribed nausea therapies or complementary products (patient interview).
• Previously undergone chemotherapy treatment (medical note observation and/or discussion with treating oncologist).
• Undergoing weekly or multi-day chemotherapy regiments (medical note observation and/or discussion with treating oncologist).

Patients found to be ineligible for temporary reasons (e.g. medication prescriptions, electrolyte imbalances or recent use of ginger) will be re-screened for eligibility prior to chemotherapy commencement.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The biostatistician (independent party - based at the NHMRC Clinical Trials Centre, University of Sydney) will notify the research assistant by telephone or email of the blinded number on the supplement label of each patient only after participants are deemed eligible.
To ensure blinding of participants, supplement and placebo capsules are over-encapsulated with a non-gelatin capsule and labelled by an independent third party, using a blinded sequence supplied by the biostatistician, prior to delivery to the study sites.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised into intervention and placebo groups (1:1) using the method of minimization, stratified by chemotherapy category (moderate vs. high emetogenicity), gender, age (<55, equal to or greater than 55 years), and by facility site. The randomization process is to be managed by an independent third party (biostatistician at the NHMRC Clinical Trials Centre, University of Sydney).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
A single site double-blind, randomised, placebo-controlled trial
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome is the difference in the impact of nausea on QoL (CIN-related QoL as assessed by FLIE, continuous scale) at day 5 (4-days post chemotherapy) between the intervention and placebo groups. It will be calculated by an independent t-test as well as repeated measures (over the 3 chemotherapy cycles), based on mean differences between groups, adjusting for baseline, using intention-to-treat principles. Multiple imputation will be used to input missing data for covariates and FLIE scores. If possible, adjusted results will be calculated using a multiple linear regression model including the stratification factors (recruitment site, emetogenicity) and other known risk factors for nausea such as gender, age, anxiety, and patient expectations of treatment.
Secondary outcomes will also be analysed at day 5 (4-days post chemotherapy) between the intervention and placebo groups and will be calculated based on mean differences, adjusting for baseline, using an independent t-test for continuous variables (global QoL, fatigue, PG-SGA score) and chi-square for categorical variables (PG-SGA global rating).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment outside Australia
Country [1] 21124 0
New Zealand
State/province [1] 21124 0
Auckland

Funding & Sponsors
Funding source category [1] 300944 0
University
Name [1] 300944 0
University of Auckland
Country [1] 300944 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
85 Park Road,
Faculty of Medical and health Sciences
Grafton.
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 301119 0
None
Name [1] 301119 0
Address [1] 301119 0
Country [1] 301119 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 301710 0
Health research Council Standing Committee on Therapeutic Trials (SCOTT)
Ethics committee address [1] 301710 0
Level 3, 110 Stanley St, Grafton, Auckland 1010
Ethics committee country [1] 301710 0
New Zealand
Date submitted for ethics approval [1] 301710 0
01/02/2019
Approval date [1] 301710 0
Ethics approval number [1] 301710 0

Summary
Brief summary
Chemotherapy-induced nausea and vomiting are typically treated with medications that effectively control vomiting, but provide limited, if any, relief from nausea. Two-thirds of chemotherapy patients internationally report chemotherapy-induced nausea (CIN), often rating it as the most disabling side-effect of treatment. Unpublished data from Auckland District Health Board (ADHB) oncology staff indicate CIN prevalence as high as 75%. The personal and social impacts of CIN are considerable. Research consistently demonstrates that CIN reduces patients’ quality of life and physical function, most significantly impairing their ability to undertake normal family and employment roles. CIN is further associated with increases in healthcare costs to patients and cancer services, which could be avoided with better CIN control. Critically, persistent CIN can delay cancer treatment and impair dose tolerance, culminating in poor treatment outcomes.
The Australian pilot data indicate that standardised ginger supplementation could be an effective adjuvant to conventional anti-nausea therapy to address CIN. The aim of this study is to investigate the efficacy, tolerability and safety of standardised adjuvant ginger on CIN in ADHB chemotherapy patients by way of a randomised, double-blind, placebo-controlled trial.
Based on Australian peer-reviewed and published protocols this project builds on their promising pilot data. It also extends an established international collaboration to a new multidisciplinary clinical and academic partnership in Auckland. If the SPICE-NZ trial demonstrates intervention effectiveness, this novel, low-cost, adjuvant for CIN could translate to clinical policy and practice, improving outcomes for patients and providing significant economic and social benefits to the health care system.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87846 0
Prof Alexandra. L McCarthy
Address 87846 0
School of Nursing
Faculty of Medical and Health Sciences
85 Park Road,
Grafton
Auckland 1023
Country 87846 0
New Zealand
Phone 87846 0
+64 09 923 2897
Fax 87846 0
Email 87846 0
alexandra.mccarthy@auckland.ac.nz
Contact person for public queries
Name 87847 0
Prof Alexandra. L McCarthy
Address 87847 0
School of Nursing
Faculty of Medical and Health Sciences
85 Park Road,
Grafton
Auckland 1023
Country 87847 0
New Zealand
Phone 87847 0
+64 09 923 2897
Fax 87847 0
Email 87847 0
alexandra.mccarthy@auckland.ac.nz
Contact person for scientific queries
Name 87848 0
Prof Alexandra. L McCarthy
Address 87848 0
School of Nursing
Faculty of Medical and Health Sciences
85 Park Road,
Grafton
Auckland 1023
Country 87848 0
New Zealand
Phone 87848 0
+64 09 923 2897
Fax 87848 0
Email 87848 0
alexandra.mccarthy@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.