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NCT Number: NCT04785989

In Vivo Metabolic Profiling of CLL (Chronic Lymphocytic Leukemia)

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.

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Key information

Conditions

Chronic Lymphocytic Leukemia Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location status: Recruiting

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Group A

  • Adult (18 years of age or older)
  • No previous history of cancer
  • Routine history of normal blood counts and vital signs
  • Documented Informed Consent

Group B

  • Adult (18 years of age or older)
  • Diagnosis of CLL with low disease burden defined as Rai stage 0 ((Lymphocytosis; no enlargement of the lymph nodes, spleen, or liver; red blood cell and platelet counts are near normal.)
  • Treatment naïve
  • Documented Informed Consent

Group C

  • Adult (18 years of age or older)
  • Diagnosis of CLL with high systemic disease burden defined as infiltration of bone marrow causing cytopenia
  • Treatment naïve
  • Able/willing to have bone marrow aspiration
  • Documented Informed Consent

Exclusion criteria

For all participants

  • Prisoners
  • Psychiatric inpatients or people who are institutionalized
  • Minor (Less than 18 years of age)
  • History of diabetes
  • Cannot be on antihyperglycemic therapy
  • Carbohydrate restricting diets: Atkins, Vegan, Ketogenic, etc.
  • Females of child bearing potential
  • Persons without decision-making capacity
  • Person who cannot read/write English
  • Not meeting inclusion criteria defined above

Treatment and study plan

[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.

Primary outcomes

  1. 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)

    It will reveal how CLL cells utilize glucose compared to non-leukemic lymphocytes and how this changes with different disease burden and site of disease. Participants will be on overnight fasting.

  2. Amount of [U-13C15N]L-glutamine incorporation into metabolites in normal and leukemic lymphocytes: LCMS pharmacokinetic analysis

    Time frame: up to 2 hours (± 5 minutes)

    It will reveal how CLL cells utilize glutamine compared to non-leukemic lymphocytes and how this changes with different disease burden and site of disease. Participants will be on overnight fasting.

Other outcomes

  1. Validate ex vivo labeling model to assay metabolism

    Time frame: 10 minutes

    Study team seek to develop a more cost-effective ex vivo model to assay metabolism under conditions closest to the physiological setting in a small amount of blood. In addition, this model will allow numerous pharmacologic interventions and may serve as a personalized ex vivo drug screening assay.

    Participants will be on overnight fasting. Cells and plasma will be separated from 5 ml of pre infused blood. Cell suspensions will be incubated at 37°C for 2hrs and intracellular and extracellular metabolites will be extracted separately for LCMS analysis.

Study contacts

Contact information is provided by the study sponsor or research team.

Cancer Connect

CONTACT

[email protected]

800-622-8922

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Registry information

Official study title

Metabolic Profiling of Leukemic Cells Through Isotope Tracing in Patients With CLL

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Mar 8, 2021
Registry last updated
Nov 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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