In Vivo Metabolic Profiling of CLL (Chronic Lymphocytic Leukemia)

Part of paid clinical trials in Madison, Wisconsin.

Sponsor
University of Wisconsin, Madison
Study ID
NCT04785989
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Accepted

Interventions

  • [U-13C]glucose — OTHER
    \[U-13C\]glucose will be administered as a bolus of 8 g (grams) over 10 minutes followed by 8 g/hour continuous infusion over 2 hours . This infusion rate will allow glucose tracer to reach sufficient enrichment without causing significant metabolic perturbation such as hyperglycemia.
  • [13C5]glutamine — OTHER
    6mg/kg of body weight of \[13C5\]glutamine will be administered as a bolus over 10 minutes (± 1 minute) followed by 6mg/kg/hr body weight continuous infusion for 2 hours through a peripheral IV catheter/line. This infusion rate will allow glutamine tracer to reach sufficient enrichment without causing significant metabolic perturbation such as hyperglycemia.

Study Details

Metabolic reprogramming has been identified as a hallmark of cancer. Almost a century after Otto Warburg initially discovered increased glycolytic activity in tumor tissue ("Warburg effect"), therapeutic targeting of cancer metabolism has become a field of intense research effort in cancer biology. A growing appreciation of metabolic heterogeneity and complexity is currently reshaping investigators "simplistic" understanding of metabolic reprogramming in cancer. Discovering metabolic vulnerabilities as new treatment targets for cancer requires systematic dissection of metabolic dependencies, fuel preferences, and underlying mechanisms in the specific physiological context. However, today's data on cancer cell metabolic signatures and heterogeneity in their physiological habitat of the human organism is sparse to non-existent representing a critical knowledge gap in designing effective metabolic therapies. Here, the investigators propose a "top-down" approach studying cancer cell metabolism in patients followed by mechanistic in-depth studies in cell culture and animal models to define metabolic vulnerabilities. Investigators will develop a metabolic tracing method to quantitatively characterize metabolic signatures and fuel preferences of leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL). Isotopic metabolic tracers are nutrients that are chemically identical to the native nutrient. Incorporated stable, non-radioactive isotopes allow investigators to follow their metabolic fate by monitoring conversion of tracer nutrients into downstream metabolites using cutting-edge metabolomics analysis. Using this method, investigators propose to test the hypothesis that leukemic lymphocytes show tissue-specific metabolic preferences that differ from non-leukemic lymphocytes and that ex vivo in-plasma labeling represents a useful model for assaying metabolic activity in leukemic cells in a patient-specific manner.

Key Dates

Start date
Jun 13, 2022
Status verified
Oct 2025
Primary completion
Oct 31, 2026
Completion
Oct 31, 2026

Study Design

Enrollment
16 participants (estimated)

Arms

  • Arm: Group A: Healthy volunteers
    Healthy volunteers are defined as people without a history of cancer
  • Arm: Group B subset-1: Treatment naïve CLL(Chronic Lymphocytic Leukemia) patients with low disease burden
    Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.
  • Arm: Group B subset-2: Treatment naïve CLL patients with low disease burden
    Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.
  • Arm: Group C:Treatment naïve CLL patients with high systemic disease burden
    Treatment naïve CLL patients with high systemic disease burden

Primary Outcome Measure

Amount of [U-13C]glucose incorporation into metabolites in normal and leukemic lymphocytes: Liquid chromatography-mass spectrometry (LCMS) pharmacokinetic analysis [ Time Frame: up to 2 hours (± 5 minutes) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of WisconsinMadisonWisconsin53705-

Find similar trials in Madison, WI

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
University of Wisconsin· Madison, WI

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