13C-Glucose Tracing of Tumour and T Cells in the Ascites of Ovarian Cancer Patients. (iMETABO)

Metabolic Tracing of Tumour and T Cells in the Ascites of Ovarian Cancer Patients

The objective of the study is to investigate the metabolism of cells in the ascites tumour microenvironment of ovarian cancer patients. This observational study involves intravenous infusion of [U-13C]glucose into patients during standard paracentesis.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Ascites
• Intervention / Treatment: Dietary supplement: [U-13C]Glucose

Detailed Description

Participants and Location:

This study will recruit up to 10 patients of at least 18 years of age with ascites due to diagnosed ovarian cancer. Eligible study patients will be screened and recruited at BC Cancer - Victoria. Paracentesis procedure and patient consent will occur at the Island Health - Royal Jubilee Hospital.

Study Design:

Participants meeting the inclusion criteria will be fitted with a continuous glucose monitor (FreeStyle Libre) before proceeding to their scheduled appointment for paracentesis. Labeled glucose will be administered via I.V. at dose of 8g of labeled glucose in 60 mL over 10 min. This is followed by 4g of labeled glucose in 30 mL over an hour.

Sample collection and processing:

During [U-13C]glucose infusions, the ascites specimens will kept on ice. Samples will be collected and analyzed by flow cytometry and mass spectrometry for states of metabolism and metabolite profiles respectively. The ascites fluid will be monitored for changes in metabolite levels.

[U-13C]glucose Product Information:

[U-13C]glucose clinical grade will be compound BC Cancer Pharmacy.

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

• Study Contact: Name: Julian J. Lum, PhD; Phone Number: 250-519-5700; Email: JLum@bccancer.bc.ca
• Study Contact Backup: Name: Jennifer Rauw, MD; Phone Number: 250-519-5500; Email: Jennifer.Rauw@bccancer.bc.ca

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada
      • Recruiting
      • Jennifer Rauw
      • Contact: Jennifer Rauw, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Adults over the age of 18 with ascites due to diagnosed ovarian cancer.

Description

Inclusion Criteria:

• Ovarian cancer
• Any stage or grade of disease
• Ascites fluid that requires draining
• Any treatment regimen
• Primary or recurrent ascites
• Understands the concept of the study and give informed consent.

Exclusion Criteria:

• Participants must not have diabetes or abnormal hemoglobin A1C levels.
• The patient's glucose levels must be between 4 - 11.1 mM before administering an infusion. This is to ensure that patients are within normal blood glucose levels, as described by Diabetes Canada.
• Participants cannot receive chemotherapy treatment during the 5 hour duration of the experiment as it may compromise the integrity of the data.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

[U-13C]glucose; All participants consented to the study will receive the [U-13C]glucose infusion and collection of ascites for research.

Dietary supplement: [U-13C]Glucose; Patients are intravenously infused with 28g of [U-13C]glucose over a 5 hour period. Briefly, [U-13C]glucose will be provided by intravenous line containing 8g of [U-13C]glucose in 60 mL over 10 min. After 10 minutes, 4g of [U-13C]glucose will be administered over an hour. This process will continue until the patient's ascites is drained, or after 5 hours. We will monitor blood glucose levels during infusions using a continuous glucose monitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieve [U-13C]Glucose enrichment in the ascites of ovarian cancer patients	Extracellular [U-13C]Glucose label enrichment in the ascites fluid (measured by mass spectrometry).	Duration of ascites paracentesis (samples collected hourly, up to 5 hours)
Compare glucose uptake and metabolic pathways in different cell populations in the ascites.	Fractional enrichment of intracellular [U-13C]Glucose and 13C labeled metabolites in T cells, myeloid cells and tumour cells (measured by mass spectrometry).	Duration of ascites paracentesis (samples collected hourly, up to 5 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlate metabolic profiles with functionality of T cells found in the ascites.	Multi-parametric flow cytometry analysis of glucose uptake, mitochondrial function, T cell phenotypes and function.	One time - Duration of ascites paracentesis

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: University of Victoria; University of Texas Southwestern Medical Center; Van Andel Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Ascites; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: H18-03615

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No