Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Longitudinal Trial

Long-term Effects Secondary to Cancer Therapy in Adults Clinical Trial

Official title:

Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Randomized Longitudinal Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02468882
• Other study ID #: ULisbon
• Status: Recruiting
• Phase: Phase 3
• First received: May 21, 2015
• Last updated: June 8, 2015
• Start date: March 2014
• Est. completion date: January 2019

Study information

• Verified date: June 2015
• Source: University of Lisbon
• Contact: Paula Ravasco, MD PhD
• Email: p.ravasco[@]medicina.ulisboa.pt
• Is FDA regulated: No
• Health authority: Portugal: Ethics Committee for Clinical Research
• Study type: Interventional

Clinical Trial Summary

Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancer. Studies identified PEITC and several active isothiocyanates in watercress extract that may have significant anticarcinogenic activity. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes, by inhibiting cell cycle progression and/or by inducing apoptosis.

These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.

Description:

The relation between cancer and nutrition has been well established; cancer builds upon damage to cellular DNA resulting from carcinogenic environmental factors, in which nutrition plays a major role. Many diet and lifestyle factors can influence the development of cancer, a disease expected to affect worldwide more than 1 in 3 people. Population studies associate a higher intake of cruciferous vegetables with a reduced risk of cancers at several locations. In 1977, a study in laboratory animals showed the potential effect of phenylethyl isothiocyanate (PEITC) to inhibit carcinogenesis. Recent studies identified several active isothiocyanates in watercress extract that may have more significant anticarcinogenic activity than PEITC alone. Potential anticarcinogenic mechanisms include: preventing carcinogen activation by inhibiting phase I enzymes such as cytochrome P450s, by increasing cells' resistance through detoxification/antioxidant enzymes; e.g. phase II enzymes (quinone reductase, glutathione S-transferases, UDP glucuronosyltransferases);, by inhibiting cell cycle progression and/or by inducing apoptosis.

Several watercress components have antigenotoxic effects in vitro resulting in reduced DNA damage and have anti-proliferative effects. These components include flavonols such as quercetin, hydroxycinnamic acids such as ferulic acid and p-coumaric acid. In HT29 colon cancer cells, an extract of watercress juice was associated with inhibition of the three stages of carcinogenesis: initiation, proliferation and metastasis. In MDA-MB-23 human breast cancer cells, watercress extract inhibited metalloproteinase-9 activity, thus suppressing the invasive potential of cancer cells. In breast cancer, epidemiological studies suggest that cruciferous vegetables may reduce cancer incidence. In animal studies, a 9-week PEITC-NAC supplemented diet vs a non-supplemented diet was significantly associated with reduction in tumour size and weight.

A recognised mechanism by which PEITC inhibits the growth and survival of established cancer cells is through the inhibition of angiogenesis. A study explored the impact of PEITC on a specific pathway central to angiogenesis by exposing human MCF7 breast cancer cells to PEITC and measuring hypoxia inducible factor (HIF) signaling activity. PEITC was shown as an effective inhibitor of HIF activity which may contribute to its anti-angiogenic and anti-cancer properties. A follow up to this experiment demonstrated that, similar to PEITC, crude watercress extracts inhibited cancer cell growth and HIF activity in vitro. Furthermore 6 to 8 hours after a significant amount dietary intake of watercress by four healthy participants, peripheral blood cells demonstrated significantly reduced HIF signalling activity, suggesting that dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway.

Of further relevance, a blind, randomized crossover study was carried out in 60 healthy volunteers instructed to consume one pack (85g) of raw watercress daily for 8 weeks. Compared to the control phase, watercress supplementation increased lymphocytes' DNA resistance to free radicals, thus reducing DNA damage. The hypothesis set out was that watercress may reduce cancer risk via decreased damage to DNA and possible effects on antioxidant status by increasing levels of plasma carotenoids.

These findings are justifiably interesting for the primary care setting and cancer primary prevention. Yet, these cellular effects of watercress supplementation may further prove useful in the modulation of cancer progression and disease recurrence, a not yet explored area. Of note, that the role of nutrition intervention in medium and long term outcomes in cancer has been demonstrated. It is today acknowledged as grade A evidence that individualized nutritional counseling and education plays a central role in improving long-term outcomes in cancer, by prolonging survival, reducing late RT toxicity and improving QoL. The present clinical trial of nutritional supplementation in cancer, intends to further explore the effects of therapeutic diets supplemented with nutraceuticals via watercress that may prove useful in DNA damage modulation, as well as in the global disease prognosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• adult breast cancer female patients consecutively referred for primary radiotherapy with curative intent

Exclusion Criteria:

• pregnancy

• cognitive impairment

• uncooperative or

• patients with any implantable electronic device (e.g. pacemaker) or internal metal material preventing BIA phase angle assessment

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Outcomes Assessor)

Related Conditions & MeSH terms

• Long-term Effects Secondary to Cancer Therapy in Adults

Intervention

Dietary Supplement:
• Watercress
100g of watercress daily during radiation therapy

Locations

Country	Name	City	State
Portugal	Hospital de Santa Maria	Lisboa

Sponsors (1)

Lead Sponsor	Collaborator
University of Lisbon

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell phase angle	as an indirect measure of cell membrane integrity, function and metabolism	Change from baseline at up to 6 weeks	No
Primary	body composition	assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA) and CT scan images; CT scans analysis will be performed in collaboration with expert groups	Change from baseline at up to 6 weeks	No
Primary	treatments' toxicity and symptoms	Assessed by the RTOG Common Toxicity Criteria, developed by the Eastern Cooperative Oncology Group (RTOG)	up to 6 weeks	No
Primary	RT induced skin dermitis	Evaluated by a radiation oncologist, using a validated toxicity scale	up to 6weeks	No
Primary	Quality of Life (QoL)	will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology	Change from baseline at up to 6 weeks	No
Primary	DNA damage	DNA damage assessment by Comet assay in lymphocytes has been used extensively as a surrogate biomarker to measure exposure to genotoxic agents and assess cancer risk in human studies by us and others. biological samples will comprise serum or plasma (1 mL) prepared from blood samples collected in Heparin tubes and urine (1 mL). Metabolomic profiles will be measured on a 700 MHz 1H NMR spectrometer equipped with a cryo-probe for enhanced sensitivity. 1H NMR spectroscopy: high throughput metabolic phenotyping is a powerful approach for characterising biochemical signatures of biological samples. We will couple high-resolution 1H NMR spectroscopy and mathematical modelling approaches to determine the metabolic profile in biological samples from patients.	Change from baseline at up to 6 weeks	No
Primary	Metabolomic profile	Metabolomics simultaneously measures thousands of low molecular weight metabolites providing holistic information on the biochemical status of the body. Previous metabolomic studies have identified cancer-associated perturbations in the metabolic phenotypes of patients. This study will explore the ability of watercress to improve the restorative effects of radiotherapy in breast cancer patients on the metabolic status towards a healthy phenotype	Change from baseline at up to 6 weeks	No
Primary	Nutritional status	assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology	Change from baseline at up to 6 weeks	No
Primary	Dietary intake	Will derive from a diet history and a 24-hour-recall food questionnaire. The software Dietplan6 (Forestfield Software Ltd 2013®, Horsham, UK) will analyze the nutrient content of foods consumed	Change from baseline at up to 6 weeks	No
Primary	Carotenoids and flavonoids	The plasma samples analysis will also include the measurement of carotenoids and flavonoids, which are present in watercress, and are related with antigenotoxic effects in vitro and have anti-proliferative effects, as demonstrated in several studies. Urine samples analysis will allow the measurement of flavonoids.	Change from baseline at up to 6 weeks	No
Secondary	Cell phase angle 2	as an indirect measure of cell membrane integrity, function and metabolism	change from 3 months at 3 years	No
Secondary	body composition 2	assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA)	change from 3 months at 3 years	No
Secondary	Quality of Life 2 (QoL2)	will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology	change from 3 months at 3 years	No
Secondary	Metabolomic profile 2	Metabolomics simultaneously measures thousands of low molecular weight metabolites providing holistic information on the biochemical status of the body. Previous metabolomic studies have identified cancer-associated perturbations in the metabolic phenotypes of patients. This study will explore the ability of watercress to improve the restorative effects of radiotherapy in breast cancer patients on the metabolic status towards a healthy phenotype	change from 3 months at 3 years	No
Secondary	Nutritional status 2	assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology	change from 3 months at 3 years	No
Secondary	Dietary intake 2	Will derive from a diet history and a 24-hour-recall food questionnaire. The software Dietplan6 (Forestfield Software Ltd 2013®, Horsham, UK) will analyze the nutrient content of foods consumed	change from 3 months at 3 years	No