PI3K Gene MutationNCT05571670
Bile Acids in Acute Insulin Resistance
An observational study of PI3K Gene Mutation and AKT Gene Mutation, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- PI3K Gene Mutation, AKT Gene Mutation, MTOR Gene Mutation
- What is being tested?
- Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jun 2022to 10 Jun 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients of any gender, without pre-existing diabetes, treated with PI3K/AKT/mTOR inhibitors for cancer according to standard of care.
Who may be able to join
- Age ≥ 18 years
- Speaks English and/ or Spanish
- Any cancer diagnosis
- Planned for treatment with:
- PI3K inhibitors
- Alpelisib
Show all 19Show fewer
- 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
Who cannot join
- Known dysglycemia
- Known diagnosis of diabetes mellitus
- Treatment with glucose-lowering medications at baseline
- Insulin
- Sulfonylureas or meglitinides
- Metformin >1000mg total daily dose
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: Bile Acid and Lipid Metabolism in Patients With Drug-induced Acute Insulin Resistance
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.
Read the 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.
- Being tested
- Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor
- Keywords
- Insulin resistance, Bile acids, Cardiovascular disease, Dyslipidemia
- Medical subject headings
- Neoplasms, Insulin Resistance, Cardiovascular Diseases, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitorDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 1-2 months
Secondary outcomes (2)
Lipid profile
The primary endpoint is the outcome of the secondary objective: namely, evaluation of the effect of PI3Ki/AKTi/mTORi-induced insulin resistance on the lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, free fatty acids) when fasting +/- after 2-hour mixed meal tolerance test
Measured: 1-2 months
Surrogate markers of BA signaling
Determine the timing and extent of PI3K/AKT/mTOR inhibitor treatment on parameters of bile acid signaling: fibroblast growth factor 19 (FGF-19) and glucagon-like peptide-1 (GLP-1). We expect that a shift in BA pool composition (especially as regards 12-HBA vs non-12-HBA) will impact differentially on FGF-19 and GLP-1 levels.
Measured: 1-2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2022
- Study start10 Jun 2022
- Primary completion10 Jun 2022
- Study completion10 Jun 2022
Why it stopped: Poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PI3K Gene MutationStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joshua Cook, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05571670
- Sponsor's protocol ID
- AAAU0504
- Status last verified
- Jan 2025
- First submitted
- 5 Oct 2022
- Last updated
- 16 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bile Acid and Lipid Metabolism in Patients With Drug-induced Acute Insulin Resistance
- ClinicalTrials.gov ID
- NCT05571670
- Acronym / sponsor ID
- AAAU0504
- Keywords
- Insulin resistance, Bile acids, Cardiovascular disease, Dyslipidemia
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Poor enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 10 Jun 2022 (actual)
- Primary completion
- 10 Jun 2022 (actual)
- Study completion
- 10 Jun 2022 (actual)
- First posted
- 7 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients treated with PI3K/AKT/mTOR inhibitors for cancer | – | Drug: Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitorPatients 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients of any gender, without pre-existing diabetes, treated with PI3K/AKT/mTOR inhibitors for cancer according to standard of care.
Key inclusion criteria (19 listed)
- Age ≥ 18 years
- Speaks English and/ or Spanish
- Any cancer diagnosis
- Planned for treatment with:
- Signed informed consent
Key exclusion criteria (17 listed)
- Known dysglycemia
- Known diagnosis of diabetes mellitus
- Treatment with glucose-lowering medications at baseline
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drug-induced acute insulin resistance due to PI3K inhibitor, AKT inhibitor, or mTOR inhibitorParticipants 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. | Drug | Patients treated with PI3K/AKT/mTOR inhibitors for cancer |
Primary outcome
Ratio of 12-HBA to non-12-HBA
Time frame: 1-2 Months
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.
Insulin resistance
Time frame: 1-2 months
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
2 secondary outcomes
Lipid profile
Time frame: 1-2 months
Surrogate markers of BA signaling
Time frame: 1-2 months
Results and safety
The study was stopped early (reason given: Poor enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PI3K Gene Mutation and AKT Gene Mutation, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Poor enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of 12-HBA to non-12-HBA (time frame: 1-2 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2025.