Bile Acids in Acute Insulin Resistance

NCT05571670 | Terminated DMC

• 1 other identifier: AAAU0504
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

PI3K Gene Mutation; AKT Gene Mutation; MTOR Gene Mutation; Cancer; Insulin Resistance

Keywords

Insulin resistance; Bile acids; Cardiovascular disease; Dyslipidemia

Outcome Measures

Primary Outcomes (2)

• Ratio of 12-HBA to non-12-HBA

  Insulin resistance is expected to cause a rise in total bile acids, but with 12-alpha-hydroxylated bile acid (12-HBA) species outpacing non-12-alpha-hydroxylated bile acid (non-12-HBA) species, leading to a rise in the 12-HBA:non-12-HBA ratio. This would indicate that insulin resistance per se is sufficient to alter 12-HBA balance, and thus 12-HBA may be a useful therapeutic target for management of the macrovascular complications of insulin resistance. BA profile and levels of BA intermediates 7-HCO and 7,12-diHCO will be measured by LC-MS/MS when fasting +/- after 2-hour mixed meal tolerance test.

  1-2 Months

• Insulin resistance

  Determine the timing and extent of PI3K/AKT/mTOR inhibitor treatment on parameters of insulin resistance: glucose, insulin, c-peptide, and adiponectin when fasting +/- following 2-hour mixed meal tolerance test

  1-2 months

Secondary Outcomes (2)

• Lipid profile

  1-2 months

• Surrogate markers of BA signaling

  1-2 months

Study Arms (1)

Patients treated with PI3K/AKT/mTOR inhibitors for cancer

Patients with cancer being treated with PI3K/AKT/mTOR inhibitors will be studied prospectively for the impact of treatment on bile acid metabolism as a function of drug-induced acute insulin resistance. Treatments will be selected by patients' treating oncologist based on standard of care.

Drug: Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor

Interventions

Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor DRUG

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.

Patients treated with PI3K/AKT/mTOR inhibitors for cancer

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples will be drawn fasting +/- after 2-hour mixed meal tolerance test immediately before and then at 2 and 4 weeks after initiation of PI3K/AKT/mTOR inhibitor treatment. Blood will also be drawn at the end of treatment if treatment concludes within 2 months of starting.

MeSH Terms

Conditions

Neoplasms; Insulin Resistance; Cardiovascular Diseases; Dyslipidemias

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medical Center

Study Record Dates

• First Submitted: October 5, 2022
• First Posted: October 7, 2022
• Study Start: June 10, 2022
• Primary Completion: June 10, 2022
• Study Completion: June 10, 2022
• Last Updated: January 16, 2025

Record last verified: 2025-01

Locations

US (1)