Bile Acids in Acute Insulin Resistance

Trial Title: Bile Acids in Acute Insulin Resistance

NCT ID: NCT05571670

Condition: PI3K Gene Mutation
AKT Gene Mutation
MTOR Gene Mutation
Cancer
Insulin Resistance

Conditions: Official terms:
Insulin Resistance
Sirolimus
MTOR Inhibitors
Temsirolimus

Conditions: Keywords:
Insulin resistance
Bile acids
Cardiovascular disease
Dyslipidemia

Study type: Observational

Overall status: Recruiting

Study design:

Time perspective: Prospective

Intervention:

Intervention type: Drug
Intervention name: Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor
Description: Participants will be treated with PI3K/AKT/mTOR inhibitors by their treating oncologist based on standard of care. This study will prospectively monitor bile acids and parameters of insulin resistance before and during treatment with these drugs.
Arm group label: Patients treated with PI3K/AKT/mTOR inhibitors for cancer

Summary: This is a prospective observational study with a primary goal of monitoring changes in circulating bile acid profiles and parameters of glucose and lipid metabolism prior, during, and after cancer treatment with agents that directly impair insulin action: PI3K inhibitors, AKT inhibitors, and mTOR inhibitors. Patients will not receive any cancer treatment specifically for the purposes of this study. Rather, this study will be based on treatment decisions made independently by participants' oncologists according to standard of care or other clinical trial protocol. This study seeks to enroll at least 25 participants each for PI3K inhibitors, mTOR inhibitors and, once available for open-label treatment, AKT inhibitors.

Detailed description: The primary objective of this study is to determine the effect of drug-induced acute insulin resistance (diaIR) on the ratio of 12α-hydroxylated bile acids (12-HBA) to 12α-hydroxylated bile acids (non-12-HBA) in cancer patients treated with phosphatidylinositol-4,5-bisphosphate kinase (PI3K) inhibitors (PI3Ki), mammalian target of rapamycin (mTOR) inhibitors (mTORi), and AKT inhibitors (AKTi) once possible. Specifically, this study will: (1) verify the induction of diaIR by monitoring changes in fasting ± postprandial blood glucose, insulin/c-peptide, and fructosamine; and (2) assess qualitative and quantitative changes in the circulating bile acid (BA) pool (including bile acid intermediary metabolites) by mass spectrometry in the fasting ± postprandial states prior to and then at 2 and 4 weeks after starting treatment. This study focuses in particular on determining changes in the 12α-hydroxylated bile acids to 12α-hydroxylated bile acids, as well as each of these subclasses and their individual substituents as a proportion of the overall BA pool.

Criteria for eligibility:

Study pop:
Adult patients of any gender, without pre-existing diabetes, treated with PI3K/AKT/mTOR inhibitors for cancer according to standard of care.

Sampling method: Non-Probability Sample
Criteria:
Inclusion Criteria: - Age ≥ 18 years - Speaks English and/ or Spanish - Any cancer diagnosis - Planned for treatment with: - PI3K inhibitors - Alpelisib - Inavolisib - Any experimental PI3K inhibitor - AKT inhibitors (if these become available for open-label use during the study course) - Afuresertib - Capivasertib - Ipatasertib - Miransertib - Uposertib - mTOR inhibitors - Everolimus - Sirolimus - Temsirolimus - Signed informed consent Exclusion Criteria: - Known dysglycemia - Known diagnosis of diabetes mellitus - Treatment with glucose-lowering medications at baseline - Insulin - Sulfonylureas or meglitinides - Metformin >1000mg total daily dose - Thiazolidinediones - SGLT2 inhibitors - GLP-1 receptor agonists - DPP4 inhibitors - Amylin mimetics - Acarbose - Significant biochemical evidence of liver dysfunction on lab tests within 30 days before starting drug that have not fallen to below the following thresholds prior to starting drug - Significant functional or anatomical abnormalities of the small intestine - Use of certain medications at baseline, within 7 days of starting cancer drug - Allergy to cow dairy or soy (only excludes from MMTT, does not exclude from fasting blood draws) - Inability to provide informed consent

Gender: All

Minimum age: 18 Years

Maximum age: 99 Years

Healthy volunteers: No

Locations:

Facility:
Name: Columbia University Medical Center

Address:
City: New York
Zip: 10032
Country: United States

Status: Recruiting

Contact:
Last name: Joshua Cook, MD

Phone: 609-694-7867
Email: jrc2175@cumc.columbia.edu

Start date: June 10, 2022

Completion date: June 10, 2026

Lead sponsor:
Agency: Columbia University
Agency class: Other

Source: Columbia University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05571670