CEST- Glucose Enhanced MRI for Metastatic Brain Tumours

NCT02796729 | Terminated Phase 2 DMC

• 1 other identifier: H16-00646
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This project will compare two MRI contrast agents in metastatic brain tumours in humans. More specifically, the investigators will compare the tumour contrast obtained using glucose versus the current standard gadolinium-based contrast agent (GBCA, gadobutrol, trade name Gadovist, will be used). First, participants will receive a glucose bolus injection followed by glucose enhanced MRI. Second, participants will receive a Gd-DTPA bolus injection followed by Gd-DTPA enhanced MRI. Both contrast studies will be performed during the same MRI study, which will be under one hour long.

Conditions

Brain Neoplasms, Malignant; Metastasis

Outcome Measures

Primary Outcomes (1)

• Integral tumour contrast generated by GBCA and glucose experiments will be assessed using Area Under Curve (AUC).

  Area Under Curve (AUC) is measured using a sequence of MR images acquired before and after contrast injection. AUC values will be compared in tumour and contralateral brain areas to calculate the integral tumour contrast generated by glucose and GBCA experiments.

  1h procedure

Secondary Outcomes (1)

• Maximum instantaneous tumour contrast generated by GBCA and glucose experiments will be assessed.

  1h procedure

Study Arms (1)

dynamic glucose enhanced MRI after D-glucose injection

EXPERIMENTAL

IV catheter preparation: Catheter will be placed in one arm. Fasting glucose levels measured with a glucometer using a 1-2 mL sample of blood. Only participants with normal fasting blood glucose levels (70-125 mg/dL) will proceed with the study. First IV catheter will monitor blood glucose every 10 min after bolus injection until it returns to normal. Second IV catheter is placed on the opposite arm for glucose infusion and GBCA (gadobutrol) infusion. Glucose infusion protocol: Occurs when the participant is in the MRI. Bolus injection of hospital grade 25g of 50% dextrose solution over 1 min is to increase blood glucose concentrations to about 3-4 times the normal level. Blood glucose levels should return to normal levels within 30 to 60 min. GBCA infusion protocol: Occurs when the participant is in the MRI; approximately 20 min after glucose infusion. Standard intravenous bolus injection of 0.1mM/kg of gadobutrol (Gadovist) at an injection rate of 5 mL/sec.

Procedure: Magnetic resonance imaging; Drug: Gadovist (Gadobutrol); Drug: 50% dextrose solution

Interventions

Magnetic resonance imaging PROCEDURE

MRI offers excellent images of the brain and is an important tool for diagnosing metastatic brain tumors. MRI scans are often used to plan treatments such as surgery and radiotherapy. When imaging participants with metastatic brain tumors, a contrast agent is often injected intravenously to highlight the relatively small tumours in the MRI. The standard metal-based MRI contrast agent is Health Canada approved and contains a material called gadolinium. MRI studies that use gadolinium-based contrast agents are called gadolinium enhanced MRI.

dynamic glucose enhanced MRI after D-glucose injection

Gadovist (Gadobutrol) DRUG

Gadobutrol (INN) (Gd-DO3A-butrol) is a gadolinium-based MRI contrast agent (GBCA).

dynamic glucose enhanced MRI after D-glucose injection

50% dextrose solution DRUG

50% Dextrose Injection, USP is a sterile, nonpyrogenic, hypertonic solution of dextrose in water for intravenous injection.

dynamic glucose enhanced MRI after D-glucose injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or females
• Between 18 and 65 years of age
• Of all ethnic groups
• BCCA participants with at least one contrast enhancing brain mass with a diameter ≥ 1 cm and consistent with metastatic carcinoma\*
• Able to give consent
• Willingness to participate in the study \* One additional healthy participant will be included in the study to perform a 'test-run' for the complicated MRI and infusion protocol.

You may not qualify if:

• Pregnancy
• Diabetes mellitus (self-reported or HbA1C ≥ 6.5%)
• Ferromagnetic implant or foreign metallic bodies (pacemaker, loose metal, etc.)
• Claustrophobia
• History of kidney disease and/or eGFR \< 60
• Abnormal fasting blood glucose (\<70mg/dL or \>125 mg/dL)
• Allergic to corn
• History of adverse reactions to gadolinium based contrast agents
• Poor performance status (Karnofsky PS\<70%)
• Previously received whole brain radiotherapy
• All lesions evident on imaging were previously treated with stereotactic radiosurgery
• The participants weigh more than 300lbs
• The participants had surgery in the last 6 weeks
• The participants have an intrauterine device
• The participants have cosmetic tattoos

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (1)

BC Cancer Agency- Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Related Publications (3)

• Chan KW, McMahon MT, Kato Y, Liu G, Bulte JW, Bhujwalla ZM, Artemov D, van Zijl PC. Natural D-glucose as a biodegradable MRI contrast agent for detecting cancer. Magn Reson Med. 2012 Dec;68(6):1764-73. doi: 10.1002/mrm.24520. Epub 2012 Oct 16.

  PMID: 23074027 BACKGROUND

• Nasrallah FA, Pages G, Kuchel PW, Golay X, Chuang KH. Imaging brain deoxyglucose uptake and metabolism by glucoCEST MRI. J Cereb Blood Flow Metab. 2013 Aug;33(8):1270-8. doi: 10.1038/jcbfm.2013.79. Epub 2013 May 15.

  PMID: 23673434 BACKGROUND

• Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, Richardson S, Goncalves M, Parkes HG, Arstad E, Thomas DL, Pedley RB, Lythgoe MF, Golay X. In vivo imaging of glucose uptake and metabolism in tumors. Nat Med. 2013 Aug;19(8):1067-72. doi: 10.1038/nm.3252. Epub 2013 Jul 7.

  PMID: 23832090 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Neoplasm Metastasis

Interventions

Magnetic Resonance Spectroscopy; gadobutrol

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Michael McKenzie

  BCCA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 13, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 28, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)