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

• ClinicalTrials.gov Identifier: NCT02468882
• Recruitment Status: Unknown
• First Posted: June 11, 2015
• Last Update Posted: June 11, 2015
• Sponsor: University of Lisbon
• Information provided by (Responsible Party): Paula Ravasco, University of Lisbon

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Long-term Effects Secondary to Cancer Therapy in Adults	Dietary Supplement: Watercress	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Outcomes Assessor)
• Official Title: Does Watercress Intake Have an Impact on Cancer Patients Outcomes: a Randomized Longitudinal Trial
• Study Start Date: March 2014
• Estimated Primary Completion Date: January 2019
• Estimated Study Completion Date: January 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group; Watercress will be tested in its natural form as a food item that will supplement the usual diet, via the prescription of watercress as whole food added daily to the usual diet. The intervention group will be asked to consume 100 grams of watercress per day, in addition to their usual diet for the total time of RT treatment. These 100 grams of watercress per day will allow the achievement of the daily "therapeutic" dose.	Dietary Supplement: Watercress; 100g of watercress daily during radiation therapy
No Intervention: Control group; The control group will receive the standard of care, thus will maintain their ad libitum diet.

Outcome Measures

Primary Outcome Measures :

1. Cell phase angle [ Time Frame: Change from baseline at up to 6 weeks ]
   as an indirect measure of cell membrane integrity, function and metabolism
2. body composition [ Time Frame: Change from baseline at up to 6 weeks ]
   assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA) and CT scan images; CT scans analysis will be performed in collaboration with expert groups
3. treatments' toxicity and symptoms [ Time Frame: up to 6 weeks ]
   Assessed by the RTOG Common Toxicity Criteria, developed by the Eastern Cooperative Oncology Group (RTOG)
4. RT induced skin dermitis [ Time Frame: up to 6weeks ]
   Evaluated by a radiation oncologist, using a validated toxicity scale
5. Quality of Life (QoL) [ Time Frame: Change from baseline at up to 6 weeks ]
   will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology
6. DNA damage [ Time Frame: Change from baseline at up to 6 weeks ]
   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.
7. Metabolomic profile [ Time Frame: Change from baseline at up to 6 weeks ]
   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
8. Nutritional status [ Time Frame: Change from baseline at up to 6 weeks ]
   assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology
9. Dietary intake [ Time Frame: Change from baseline at up to 6 weeks ]
   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
10. Carotenoids and flavonoids [ Time Frame: Change from baseline at up to 6 weeks ]
    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.

Secondary Outcome Measures :

1. Cell phase angle 2 [ Time Frame: change from 3 months at 3 years ]
   as an indirect measure of cell membrane integrity, function and metabolism
2. body composition 2 [ Time Frame: change from 3 months at 3 years ]
   assessed by tetrapolar multifrequency Bioimpedance Analysis (BIA)
3. Quality of Life 2 (QoL2) [ Time Frame: change from 3 months at 3 years ]
   will be assessed by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30), validated for Oncology
4. Metabolomic profile 2 [ Time Frame: change from 3 months at 3 years ]
   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
5. Nutritional status 2 [ Time Frame: change from 3 months at 3 years ]
   assessed by the method Patient-Generated Subjective Global Assessment, specific and validated for Oncology
6. Dietary intake 2 [ Time Frame: change from 3 months at 3 years ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Paula Ravasco, MD PhD; p.ravasco@medicina.ulisboa.pt

Locations

Portugal

Hospital de Santa Maria; Recruiting

Lisboa, Portugal

Contact: Paula Ravasco, PhD p.ravasco@medicina.ulisboa.pt

Sponsors and Collaborators

University of Lisbon

More Information

• Responsible Party: Paula Ravasco, Principal Investigator, University of Lisbon
• ClinicalTrials.gov Identifier: NCT02468882
• Other Study ID Numbers: ULisbon
• First Posted: June 11, 2015
• Last Update Posted: June 11, 2015
• Last Verified: June 2015

Keywords provided by Paula Ravasco, University of Lisbon:

Breast cancer; Radiotherapy; Toxicity; Outcomes; Watercress