Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12616001532493
Ethics application status
Approved
Date submitted
18/10/2016
Date registered
7/11/2016
Date last updated
20/01/2020
Date data sharing statement initially provided
20/01/2020
Date results information initially provided
20/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Interaction between inulin supplementation and cyclophosphamide therapy in patients with breast cancer
Scientific title
Expression of gluthatione S-Transferase isoforms, GSTT1, GSM1 and GSTP1 in women with breast cancer undergoing neoadjuvant chemotherapy and inulin supplementation.
Secondary ID [1] 290285 0
None
Universal Trial Number (UTN)
U1111-1188-5265
Trial acronym
GICBC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast cancer 300521 0
Cachexy 300522 0
Chemotherapy toxicity 300523 0
Condition category
Condition code
Cancer 300382 300382 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Breast cancer female patients will be suplemented with inulin (15g/day) upon cyclofosfamide therapy. This supplementation will be performed daily for 21 days, it will start the day after the administration of cyclofosfamide (regardless the combination with other chemotherapeutic agents or the therapy round).
Inulin will be given as oral powder mixed in 250mL of water. In order to monitor adherence a food diary will be used as well as social networks (WhatsApp and Facebook). Moreover, hospital records of laboratory tests for albumin, transferrin and hemoglobin will be considered.
Intervention code [1] 296089 0
Treatment: Other
Comparator / control treatment
There will be a control group (n=19) that will receive maltodextrin instead of inulin for the same period of supplementation (21 days).
Control group
Placebo

Outcomes
Primary outcome [1] 299846 0
The change in GSTP1 mRNA expression in lymphocytes will be analyzed by qPCR.
Timepoint [1] 299846 0
Measures will be perfomed previuosly (day 0) and after inulin supplementation (21 days).
Primary outcome [2] 299847 0
The change in GSTM1 mRNA expression in lymphocytes will be analyzed by qPCR.
Timepoint [2] 299847 0
Measures will be perfomed previuosly (day 0) and after inulin supplementation (21 days).
Primary outcome [3] 299992 0
The change in GSTT1 mRNA expression in lymphocytes will be analyzed by qPCR.
Timepoint [3] 299992 0
Measures will be perfomed previuosly (day 0) and after inulin supplementation (21 days).
Secondary outcome [1] 328297 0
Determination of body mass index will be performed using an InBody230 bioimpedance apparatus.
Timepoint [1] 328297 0
The analysis will be performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.
Secondary outcome [2] 328765 0
Presence of gastrointestinal (nausea, vomit, diarrea) adverse events. This will be perfomed using "The service daily report of adverse events of the ISSEMYM Cancer Center".
Timepoint [2] 328765 0
This evaluation will be performed upon cyclophosphamide and inulin exposure and after last day of inulin supplementation (day 22).
Secondary outcome [3] 328766 0
Percentage of body fat mass will be determined using a Inbody230 bioimpedance apparatus.
Timepoint [3] 328766 0
The analysis is performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.
Secondary outcome [4] 328794 0
Lean mass percentage will be determined using a InBody230 bioimpedance apparatus
Timepoint [4] 328794 0
The analysis is performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.
Secondary outcome [5] 328795 0
Lean mass distribution will evaluated using a Inbody230 bioimpedance apparatus.
Timepoint [5] 328795 0
The analysis is performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.
Secondary outcome [6] 328796 0
Body water content will be evaluated using a Inbody230 bioimpedance apparatus.
Timepoint [6] 328796 0
The analysis will be performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.
Secondary outcome [7] 328797 0
Body fat distribution will be evaluated using a InBody230 bioimpedance apparatus.
Timepoint [7] 328797 0
The analysis is performed 1 day before cyclophosphamide exposure, and on day 1 once supplementation is finished.

Eligibility
Key inclusion criteria
Patients with clinical diagnosis of breast cancer, with score "0" according to the scale "Eastern Cooperative Oncology Group" (ECOG) .
Patients who agree to participate and provide the required information.
Patients with chemotherapy scheme with cyclophosphamide alone or in combination with methotrexate, 5-fluorouracil and doxorubicin.
Minimum age
34 Years
Maximum age
70 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with an ECOG score greater than or equal to 1.
Patients who do not sign informed consent.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Coin tossing
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size: non probabilistic, depending on number of patients registered at the hospital that are under cyclophosphamide therapy.
Analysis of GST mRNA expression: Mann Whitney U test
Adverse events: odds ratio, chi-squared
BMI: 2 way ANOVA
Fat and lean mass distribution as %: Friedman test
Content of water as %: Friedman test

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2016
Actual
9/01/2017
Date of last participant enrolment
Anticipated
Actual
9/05/2017
Date of last data collection
Anticipated
29/12/2017
Actual
30/06/2017
Sample size
Target
60
Accrual to date
Final
40
Recruitment outside Australia
Country [1] 8302 0
Mexico
State/province [1] 8302 0
Estado de Mexico

Funding & Sponsors
Funding source category [1] 294680 0
University
Name [1] 294680 0
Reseacrh Board of Universidad Autonoma del Estado de Mexico (UAEMEX), grant # 4319/2017CI
Country [1] 294680 0
Mexico
Funding source category [2] 294812 0
University
Name [2] 294812 0
Centro de Investigacion Medica (CICMED)
Country [2] 294812 0
Mexico
Primary sponsor type
University
Name
Universidad Autonoma del Estado de Mexico- Facultad de Medicina
Address
Paseo Tollocan esq. Jesus Carranza w/o number, ZC 50180
Toluca, Estado de Mexico
Country
Mexico
Secondary sponsor category [1] 293528 0
Hospital
Name [1] 293528 0
Centro Oncologico ISSEMYM
Address [1] 293528 0
Avenida Solidaridad Las Torres #101, Col. del Parque, ZC50180
Toluca, Estado de Mexico
Country [1] 293528 0
Mexico

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296105 0
Ethics Commitee of the "Centro Oncologico ISSEMYM"
Ethics committee address [1] 296105 0
Avenida Solidaridad Las Torres #101, Col. del Parque, ZC 50180 Toluca, Estado de Mexico
Ethics committee country [1] 296105 0
Mexico
Date submitted for ethics approval [1] 296105 0
02/05/2016
Approval date [1] 296105 0
26/05/2016
Ethics approval number [1] 296105 0
COE-UEI-/08/PT/2016

Summary
Brief summary
Cyclophosphamide is one of the major drugs used in the treatment of breast cancer, however it has adverse effects that influence the quality of life, the response to cancer therapy and disease prognosis. The family of enzymes "Glutathione S-transferase" (GST) is essential for carrying out detoxification reactions from cyclophosphamide chemotherapy, allowing proper excretion of the drug. For this reason these enzymes are essential in the occurrence and degree of adverse effects resulting from drug chemotherapy. However, little is known about chemotherapy adjuvants to reduce the appearance of side effects such as leukopenia, nausea, vomiting, diarrhea and anorexia. In particular, inulin, an indigestible carbohydrate, generates short-chain fatty acids (SCFA) through colonic fermentation. SCFA may decrease the progression of leukemia in vitro, diarrheal episodes and anorexia. They also increase life expectancy by 70% in animal models treated with cyclophosphamide and synergistically supplemented with inulin. It also has important benefits such as stimulating the growth of probiotics in the colon like Bifidobacterium and Lactobacillus, and decreasing pathogenic microorganisms like Clostridium coccoides. Moreover, inulin fermentation enhances mucus production, ion absorption, bicarbonate formation in HIV patients and decreased serum triglycerides in patients with hypercholesterolemia. Consequently, these substances modulate immune function, possibly by improving health, quality and life expectancy. The hypothesis of this study is that inulin supplementation after cyclophosphamide therapy in patients with breast cancer modulates GSTT1, GSTM1 and GSTP1 mRNA and reduces gastrointestinal adverse reactions. The aims of this study are: 1. To determine whether mRNA of GSTT1, GSTM1 and GSTP1 in lymphocytes from patients under cyclophosphamide therapy is modified upon inulin supplementation; 2. To determine whether inulin supplementation reduces gastrointestinal adverse effect of cyclophosphamide therapy. In order to prove that, we designed a randomized triple blind study where a group of female breast cancer patients from the ISSEMyM State Cancer Center will be supplemented with inulin (15g/day) for 21 days after cyclophosphamide administration. Simultaneously, a second group of patients will receive maltodextrine for the same period of time as a control. The results of this study will provide insights about the utilization of inulin as a potential prebiotic adjuvant during chemotherapy and the mechanistic role of GST in the detoxification process upon cyclophosphamide exposure in humans.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1182 1182 0 0
/AnzctrAttachments/371615-Bioethic approval GST-inulin.pdf (Ethics approval)

Contacts
Principal investigator
Name 69518 0
Prof Alexandra Estela Soto-Pina
Address 69518 0
Facultad de Medicina-Universidad Autonoma del Estado de Mexico
Paseo Tollocan esq. Jesus Carranza w/o number, ZC 50180 Toluca, Estado de Mexico
Country 69518 0
Mexico
Phone 69518 0
+52 722 2173552 ext 122
Fax 69518 0
Email 69518 0
[email protected]
Contact person for public queries
Name 69519 0
Ms Yizel Becerril Alarcón
Address 69519 0
Facultad de Medicina-Universidad Autonoma del Estado de Mexico
Paseo Tollocan esq. Jesus Carranza w/o number, ZC 50180 Toluca, Estado de Mexico
Country 69519 0
Mexico
Phone 69519 0
+52 722 5689666
Fax 69519 0
Email 69519 0
[email protected]
Contact person for scientific queries
Name 69520 0
Prof Saúl Campos Gómez
Address 69520 0
Centro Oncológico Estatal ISSEMYM
Av. Solidaridad Las Torres No. 101, Esq. Prolongación Benito Juárez. Col. Del Parque.
50180 Toluca, Estado de Mexico
Country 69520 0
Mexico
Phone 69520 0
+52 55 2755 7562
Fax 69520 0
Email 69520 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Yizel Becerril-Alarcón, Saúl Campos-Gómez, Juan J.... [More Details] 371615-(Uploaded-05-11-2019-02-29-05)-Journal results publication.pdf

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInulin supplementation reduces systolic blood pressure in women with breast cancer undergoing neoadjuvant chemotherapy.2019https://dx.doi.org/10.1155/2019/5707150
N.B. These documents automatically identified may not have been verified by the study sponsor.