Obesity-Associated Insulin ResistancePhase 1NCT04329806
Sympathetic Mechanisms in the Cardiovascular and Metabolic Alterations of Obesity
A Phase 1 study testing Moxonidine 0.2 MG and Amlodipine 5 MG in people with Obesity-Associated Insulin Resistance, run by Italo Biaggioni at 1 site in United States.
Trial summary
The purpose of this study is to study the role of sympathetic mechanisms involved in chronic regulation of cardiovascular and metabolic abnormalities seen in obesity. The investigators will study the effects chronic sympathetic inhibition on insulin sensitivity, inflammation and endothelial function in obese… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity-Associated Insulin Resistance
- What is being tested?
- Moxonidine 0.2 MG and Amlodipine 5 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Feb 2021to 27 Jul 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females of all races between 18 and 60 years of age
- Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication.
- Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.
- Able and willing to provide informed consent.
Who cannot join
- Pregnancy or breast feeding
- Current smokers or history of heavy smoking (>2 packs/day)
- History of alcohol or drug abuse
- Previous allergic reaction to study medications
- Evidence of type I diabetes
- Cardiovascular disease other than hypertension
Show all 12Show fewer
- History of serious cerebrovascular disease
- History or presence of immunological or hematological disorders
- Impaired renal function
- Treatment with any investigational drug in the 1 month preceding the study
- Inability to give, or withdraw, informed consent
- Other factors which in the investigator's opinion would prevent the subject from completing the protocol
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to study the role of sympathetic mechanisms involved in chronic regulation of cardiovascular and metabolic abnormalities seen in obesity. The investigators will study the effects chronic sympathetic inhibition on insulin sensitivity, inflammation and endothelial function in obese hypertensive human subjects.
Read the detailed description
Continuing Review (CR, 2021/08/04) Update: Removal of the angiotensin receptor blockade arm of the study
The presence of obesity increases the risk for hypertension and diabetes, in part due to the development of insulin resistance. Obesity is also associated with sympathetic activation and the overarching hypothesis is that sympathetic activation contributes to insulin resistance with impairment of its vascular and metabolic actions. Preliminary studies suggest that 1) Blood pressure can be normalized by autonomic blockade in obese hypertensives, 2) Sympathetic activation provides no metabolic benefit because the increase in resting energy expenditure associated with obesity is due to an increase in fat free mass rather than sympathetic activation. On the contrary, autonomic blockade: 3) Improves insulin sensitivity in obese hypertensives, 4) Reverses their impaired NO-mediated dilation, and 5) Reduces plasma isoprostanes, a measure of oxidative stress. Furthermore, these abnormalities are interrelated in negative feedback loops, whereby inflammation/oxidative stress impairs nitric oxide mechanisms, which in turn reduces insulin-mediated vasodilation important for substrate delivery, thus contributing to insulin resistance; insulin resistance leads to compensatory increases in insulin levels, which contributes to further sympathetic activation. Current treatment guidelines do not specifically address the treatment of obesity hypertension, and do not target sympathetic activation as a first line approach. It is important, therefore, to determine whether or not targeting sympathetic activation offers unique advantages in the treatment of obesity hypertension over current approaches. The investigators propose a proof-of-concept mechanistic study comparing the metabolic, vascular, and anti-inflammatory effects of sympathetic inhibition, calcium channel blockade and angiotensin receptor blockade in obesity hypertension. The investigators will test the hypotheses that sympathetic activation contributes to 1) metabolic insulin resistance, which impairs the suppression of endogenous glucose production and the stimulation of glucose uptake normally provided by insulin, 2) vascular insulin resistance, which impairs insulin-mediated vasodilation and microvascular recruitment that normally promote glucose uptake, and 3) inflammation and oxidative stress, which contribute to insulin resistance and hypertension. The proposed studies will gauge the contribution of sympathetic activation to the cardiovascular and metabolic complications of obesity and provide the mechanistic insight to determine whether or not it should foster the efforts currently under way to develop novel therapies targeting sympathetic activation for hypertension.
- Conditions
- Obesity-Associated Insulin Resistance
- Being tested
- Moxonidine 0.2 MG, Amlodipine 5 MG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moxonidine 0.2 MGDrug
Moxonidine 0.2 MG twice daily
Amlodipine 5 MGDrug
Amlodipine 5 MG twice daily
| Study group | Role | What they receive |
|---|---|---|
| Moxonidine | Experimental | Moxonidine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks Receives: Drug: Moxonidine 0.2 MG |
| Amlodipine | Active comparator | Amlodipine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks Receives: Drug: Amlodipine 5 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin Sensitivity
Dose response curve to insulin (measure as glucose infusion rate, mg/kg/min)
Measured: 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start23 Feb 2021
- Primary completion27 Jul 2022
- Study completion27 Jul 2022
Why it stopped: Study being replaced by crossover design
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Obesity-Associated Insulin ResistanceStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italo Biaggioni
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04329806
- Sponsor's protocol ID
- 190479
- Other IDs
- R01HL149386
- Status last verified
- Aug 2025
- First submitted
- 16 Mar 2020
- Last updated
- 5 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sympathetic Mechanisms in the Cardiovascular and Metabolic Alterations of Obesity
- ClinicalTrials.gov ID
- NCT04329806
- Acronym / sponsor ID
- 190479
- Conditions
- Obesity-Associated Insulin Resistance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study being replaced by crossover design
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Italo BiaggioniUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 23 Feb 2021 (actual)
- Primary completion
- 27 Jul 2022 (actual)
- Study completion
- 27 Jul 2022 (actual)
- First posted
- 1 Apr 2020 (actual)
- Results
- Posted 19 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to study the role of sympathetic mechanisms involved in chronic regulation of cardiovascular and metabolic abnormalities seen in obesity. The investigators will study the effects chronic sympathetic inhibition on insulin sensitivity, inflammation and endothelial function in obese hypertensive human subjects.
Detailed description
Continuing Review (CR, 2021/08/04) Update: Removal of the angiotensin receptor blockade arm of the study
The presence of obesity increases the risk for hypertension and diabetes, in part due to the development of insulin resistance. Obesity is also associated with sympathetic activation and the overarching hypothesis is that sympathetic activation contributes to insulin resistance with impairment of its vascular and metabolic actions. Preliminary studies suggest that 1) Blood pressure can be normalized by autonomic blockade in obese hypertensives, 2) Sympathetic activation provides no metabolic benefit because the increase in resting energy expenditure associated with obesity is due to an increase in fat free mass rather than sympathetic activation. On the contrary, autonomic blockade: 3) Improves insulin sensitivity in obese hypertensives, 4) Reverses their impaired NO-mediated dilation, and 5) Reduces plasma isoprostanes, a measure of oxidative stress. Furthermore, these abnormalities are interrelated in negative feedback loops, whereby inflammation/oxidative stress impairs nitric oxide mechanisms, which in turn reduces insulin-mediated vasodilation important for substrate delivery, thus contributing to insulin resistance; insulin resistance leads to compensatory increases in insulin levels, which contributes to further sympathetic activation. Current treatment guidelines do not specifically address the treatment of obesity hypertension, and do not target sympathetic activation as a first line approach. It is important, therefore, to determine whether or not targeting sympathetic activation offers unique advantages in the treatment of obesity hypertension over current approaches. The investigators propose a proof-of-concept mechanistic study comparing the metabolic, vascular, and anti-inflammatory effects of sympathetic inhibition, calcium channel blockade and angiotensin receptor blockade in obesity hypertension. The investigators will test the hypotheses that sympathetic activation contributes to 1) metabolic insulin resistance, which impairs the suppression of endogenous glucose production and the stimulation of glucose uptake normally provided by insulin, 2) vascular insulin resistance, which impairs insulin-mediated vasodilation and microvascular recruitment that normally promote glucose uptake, and 3) inflammation and oxidative stress, which contribute to insulin resistance and hypertension. The proposed studies will gauge the contribution of sympathetic activation to the cardiovascular and metabolic complications of obesity and provide the mechanistic insight to determine whether or not it should foster the efforts currently under way to develop novel therapies targeting sympathetic activation for hypertension.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Moxonidine | Experimental | Drug: Moxonidine 0.2 MGMoxonidine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks |
| Amlodipine | Active comparator | Drug: Amlodipine 5 MGAmlodipine to be administered at a dose to produce a decrease in BP of at least 20% of baseline for 9 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females of all races between 18 and 60 years of age
- Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg or currently on antihypertensive medication.
- Obesity will be defined as having a body mass index (BMI) ≥ 30 kg/m2.
- Able and willing to provide informed consent.
Key exclusion criteria (12 listed)
- Pregnancy or breast feeding
- Current smokers or history of heavy smoking (>2 packs/day)
- History of alcohol or drug abuse
- Previous allergic reaction to study medications
- Evidence of type I diabetes
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 |
|---|---|---|
| Moxonidine 0.2 MGMoxonidine 0.2 MG twice daily | Drug | Moxonidine |
| Amlodipine 5 MGAmlodipine 5 MG twice daily | Drug | Amlodipine |
Primary outcome
Insulin Sensitivity
Time frame: 6 hours
Dose response curve to insulin (measure as glucose infusion rate, mg/kg/min)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Italo Biaggioni, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Moxonidine 0.2 MG and Amlodipine 5 MG in people with Obesity-Associated Insulin Resistance, run by Italo Biaggioni 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 12 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 5 Sep 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Insulin Sensitivity (time frame: 6 hours). 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 5 Sep 2025.