Insulin ResistanceNCT03039647
Insulin Resistance and Accelerated Cognitive Aging
An observational study of Insulin Resistance, run by Stanford University at 1 site in United States.
Trial summary
Premature and accelerated brain aging trajectories have been observed among people with metabolic dysfunction, but mechanisms of these altered trajectories are not understood. Insulin resistance (IR) is known to change with age and affect cognition in older and elderly adults as well as in patients with mood… Read more about this study
- Who is it for?
- Ages 25 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- How many people
- 126 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2017to 1 May 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 25 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: The investigators will consent and enroll 160 medically stable men and women in and around Stanford. Stanford will be the only study site. Subjects will be 25-50 years old, with a body mass index (BMI) of 25 to 35kg/m2, and will have at least 12 years of education.
Who may be able to join
- Between 25 and 50 years of age
- BMI of 25 to 33 kg/m^2
- At least 12 years of education
- All subjects will be medically stable (i.e. no uncontrolled or poorly controlled medical illnesses), cognitively intact as defined by Mini Mental Status Exam (MMSE) score of > 27, and will have adequate visual and auditory acuity to allow for cognitive testing. Glycemic history will be collected together with other pertinent medical information from primary care providers.
Who cannot join
- Diagnosis of possible or probably dementia, MCI, or any other dementia
- Evidence of cognitive decline by MMSE < 27 or self-reported significant decline in memory within the past year (per the Memory Function Questionnaire)
- History of Type 1 or Type 2 Diabetes
- Fasting plasma glucose > 126 mg/dL
- History of significant cardiovascular disease or myocardial infarction, cerebrovascular/pulmonary disease, cancer, untreated hypothyroidism, unstable or untreated hypertension, history of head trauma, MRI-contraindications (i.e. metal in body, claustrophobia), premature birth (which may affect MRI findings), history of neurological disorder (ischemic attacks, carotid bruits, or lacunes upon MRI scan), or evidence of neurological or other physical illness that could produce cognitive deterioration
- Use of any drug that may significantly affect the SSPG or cognitive testing results (specifically: centrally active beta-blockers, narcotics, clonidine, antipsychotics, benzodiazepines, systemic corticosteroids, medications with significant cholinergic or anticholinergic effects, anti-convulsants, anti-diabetics, or anti-cholesterol medications)
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- Drug or alcohol abuse or dependence within the past 6 months, or positive urine toxicology screen for illicit substances at eligibility screening
- History of mental illness, with the exception of past mood disorder, or evidence of acute depression as determined by a 17-item Hamilton Depression Rating Scale (HDRS-17) score of 8 or more
- Participants with history of mood disorder must be in remission for at least 6 months prior to study entry
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford Psychiatry Building
Stanford, California, 94305
About this study
Premature and accelerated brain aging trajectories have been observed among people with metabolic dysfunction, but mechanisms of these altered trajectories are not understood. Insulin resistance (IR) is known to change with age and affect cognition in older and elderly adults as well as in patients with mood disorders. The main purpose of the study is to describe the developmental trajectory of cognitive and neural biomarkers across the spectrum of metabolic dysfunction in overweight/obese adults younger than 50 years of age. The innovative study design will allow the investigators to examine cognitive outcome development over a 25-year span without an investment into the longitudinal observation of changes in cognition and neural function.
Read the detailed description
Premature and accelerated brain aging trajectories started to be recognized in cognitive and neural responses, but specific mechanisms for the course of cognitive aging remain to be elucidated. Insulin resistance (IR) is known to change with age, affect cognition in older and elderly adults as well as in patients with affective disorders. It is unknown whether IR can predict cognitive decline in individuals younger than age 50 without overt mental illness. Studies in younger adults afford a unique opportunity to assess whether IR mediates cognitive and correlating neural processes decades before the manifestation of cognitive decline. The investigators propose to use an innovative accelerated longitudinal design (ALD) to characterize trajectories of cognitive and neural biomarkers and to: 1) describe baseline cognitive and neural biomarkers of brain function across the spectrum of IR in persons ages 25-50; 2) assess how the baseline IR and change in IR at a younger age affects the pattern of decline in cognitive and neural biomarkers and 3) explore the effects of baseline IR on changes in cognitive and neural variables of interest as moderated by non-modifiable risk factors for cognitive decline (gender, and APOE4/family history of AD). The current proposal aims to describe the developmental trajectory of cognitive and neural biomarkers across the spectrum of metabolic dysfunction in overweight/obese adults younger than 50 years of age. Utilizing an accelerated longitudinal design (ALD) we will recruit overweight/obese individuals (total N=160) aged 25-50. Based on semi-longitudinal data, this design will allow us to examine outcome development over 25 years between ages 25-50 after 3-year follow-up. All subjects will undergo baseline qualitative measure of IR, cognitive assessments and multimodal magnetic resonance imaging (MMRI). Neuropsychological evaluation will focus on cognitive flexibility/set shifting tests reflecting hippocampal connectivity to the medial prefrontal region. MMRI will include memory-related hippocampal function and connectivity (measured with task- and resting-state fMRI) and hippocampal volumes. The ALD design will allow investigation of the relation between cognitive performance and a corresponding neural response across the IR spectrum over a long period of time and the predictive value of IR of long-term trajectories of change in cognitive and neural biomarkers over span of 25 years.
- Conditions
- Insulin Resistance
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Entry Point IR (SSPG, HOMA-IR) | All subjects will undergo baseline indirect (HOMA-IR) and direct (SSPG) measures of IR. The investigators hypothesize that a higher entry point IR will predict steeper decline in memory and executive function performance and hippocampal connectivity. | |
| Change in IR (HOMA-IR) | The investigators predict that change in IR (as measured by HOMA-IR) will predict the pattern of decline in memory and executive function performance and hippocampal connectivity. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in hippocampal connectivity
This will be assessed by MRI and cognitive assessments.
Measured: Change in hippocampal connectivity from entry point to exit point three years later
Secondary outcomes (2)
Change in hippocampal volume
This will be determined by MRI analysis.
Measured: Change in hippocampal volume from entry point to exit point three years later
Change in memory-related functional activation
This will be determined by MRI analysis.
Measured: Change in memory-related functional activation from entry point to exit point three years later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start1 Jan 2017
- Primary completion1 May 2022
- Study completion1 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by Stanford 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natalie Rasgon, Stanford University
- Investigators
- Natalie Rasgon, M.D., Ph.D., Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03039647
- Sponsor's protocol ID
- 38733
- Status last verified
- May 2022
- First submitted
- 26 Jan 2017
- Last updated
- 9 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin Resistance and Accelerated Cognitive Aging
- ClinicalTrials.gov ID
- NCT03039647
- Acronym / sponsor ID
- 38733
- Conditions
- Insulin Resistance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 126 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 1 May 2022 (actual)
- Study completion
- 1 May 2022 (actual)
- First posted
- 1 Feb 2017 (estimated)
- 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.
Premature and accelerated brain aging trajectories have been observed among people with metabolic dysfunction, but mechanisms of these altered trajectories are not understood. Insulin resistance (IR) is known to change with age and affect cognition in older and elderly adults as well as in patients with mood disorders. The main purpose of the study is to describe the developmental trajectory of cognitive and neural biomarkers across the spectrum of metabolic dysfunction in overweight/obese adults younger than 50 years of age. The innovative study design will allow the investigators to examine cognitive outcome development over a 25-year span without an investment into the longitudinal observation of changes in cognition and neural function.
Detailed description
Premature and accelerated brain aging trajectories started to be recognized in cognitive and neural responses, but specific mechanisms for the course of cognitive aging remain to be elucidated. Insulin resistance (IR) is known to change with age, affect cognition in older and elderly adults as well as in patients with affective disorders. It is unknown whether IR can predict cognitive decline in individuals younger than age 50 without overt mental illness. Studies in younger adults afford a unique opportunity to assess whether IR mediates cognitive and correlating neural processes decades before the manifestation of cognitive decline. The investigators propose to use an innovative accelerated longitudinal design (ALD) to characterize trajectories of cognitive and neural biomarkers and to: 1) describe baseline cognitive and neural biomarkers of brain function across the spectrum of IR in persons ages 25-50; 2) assess how the baseline IR and change in IR at a younger age affects the pattern of decline in cognitive and neural biomarkers and 3) explore the effects of baseline IR on changes in cognitive and neural variables of interest as moderated by non-modifiable risk factors for cognitive decline (gender, and APOE4/family history of AD). The current proposal aims to describe the developmental trajectory of cognitive and neural biomarkers across the spectrum of metabolic dysfunction in overweight/obese adults younger than 50 years of age. Utilizing an accelerated longitudinal design (ALD) we will recruit overweight/obese individuals (total N=160) aged 25-50. Based on semi-longitudinal data, this design will allow us to examine outcome development over 25 years between ages 25-50 after 3-year follow-up. All subjects will undergo baseline qualitative measure of IR, cognitive assessments and multimodal magnetic resonance imaging (MMRI). Neuropsychological evaluation will focus on cognitive flexibility/set shifting tests reflecting hippocampal connectivity to the medial prefrontal region. MMRI will include memory-related hippocampal function and connectivity (measured with task- and resting-state fMRI) and hippocampal volumes. The ALD design will allow investigation of the relation between cognitive performance and a corresponding neural response across the IR spectrum over a long period of time and the predictive value of IR of long-term trajectories of change in cognitive and neural biomarkers over span of 25 years.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entry Point IR (SSPG, HOMA-IR) | – | –All subjects will undergo baseline indirect (HOMA-IR) and direct (SSPG) measures of IR. The investigators hypothesize that a higher entry point IR will predict steeper decline in memory and executive function performance and hippocampal connectivity. |
| Change in IR (HOMA-IR) | – | –The investigators predict that change in IR (as measured by HOMA-IR) will predict the pattern of decline in memory and executive function performance and hippocampal connectivity. |
Who may qualify
- Ages
- 25 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- The investigators will consent and enroll 160 medically stable men and women in and around Stanford. Stanford will be the only study site. Subjects will be 25-50 years old, with a body mass index (BMI) of 25 to 35kg/m2, and will have at least 12 years of education.
Key inclusion criteria (4 listed)
- Between 25 and 50 years of age
- BMI of 25 to 33 kg/m^2
- At least 12 years of education
- All subjects will be medically stable (i.e. no uncontrolled or poorly controlled medical illnesses), cognitively intact as defined by Mini Mental Status Exam (MMSE) score of > 27, and will have adequate visual and auditory acuity to allow for cognitive testing. Glycemic history will be collected together with other pertinent medical information from primary care providers.
Key exclusion criteria (9 listed)
- Diagnosis of possible or probably dementia, MCI, or any other dementia
- Evidence of cognitive decline by MMSE < 27 or self-reported significant decline in memory within the past year (per the Memory Function Questionnaire)
- History of Type 1 or Type 2 Diabetes
- Fasting plasma glucose > 126 mg/dL
- History of significant cardiovascular disease or myocardial infarction, cerebrovascular/pulmonary disease, cancer, untreated hypothyroidism, unstable or untreated hypertension, history of head trauma, MRI-contraindications (i.e. metal in body, claustrophobia), premature birth (which may affect MRI findings), history of neurological disorder (ischemic attacks, carotid bruits, or lacunes upon MRI scan), or evidence of neurological or other physical illness that could produce cognitive deterioration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in hippocampal connectivity
Time frame: Change in hippocampal connectivity from entry point to exit point three years later
This will be assessed by MRI and cognitive assessments.
2 secondary outcomes
Change in hippocampal volume
Time frame: Change in hippocampal volume from entry point to exit point three years later
Change in memory-related functional activation
Time frame: Change in memory-related functional activation from entry point to exit point three years later
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2022.
- Individual participant dataSharing planned: No
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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.
Natalie Rasgon, M.D., Ph.D. principal investigator
Stanford University
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 Insulin Resistance, run by Stanford 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 4 inclusion and 9 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: finished, as of the sponsor's last update on 9 May 2022. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in hippocampal connectivity (time frame: Change in hippocampal connectivity from entry point to exit point three years later). 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 9 May 2022.