OBESITYPhase 1NCT00179023
The Autonomic Nervous System and Obesity
A Phase 1 study testing Trimethaphan and Pseudoephedrine in people with OBESITY and HYPERTENSION, run by Vanderbilt University at 1 site in United States.
Trial summary
In its simplest terms, obesity is the results of a positive balance between food intake and energy expenditure (EE). I.e., we take in more energy, in the form of food, than we expend, e.g., by exercise. In our sedentary society, resting EE accounts for most of total energy expenditure. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- OBESITY, HYPERTENSION, PURE AUTONOMIC FAILURE
- What is being tested?
- Trimethaphan and Pseudoephedrine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2003to Jan 2017
- Phase
- Phase 1
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy normal (BMI <= 25 Kg/m2), obese (BMI between 30 and 40)volunteers, lean hypertensive (BMI 20-28 Kg/m2), and obese hypertensive (BMI between 30 and 40)
- Ages 18-60
- Patients with pure autonomic failure and multiple system atrophy ages 18-80, referred to our service for the diagnosis and treatment of their condition, and their age sex-matched sedentary, healthy controls ages 18-80
Who cannot join
- All medical students
- Pregnant women
- Heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction, glaucoma
- History of serious allergies or asthma
- Subjects using beta-blockers
Trial locations and contacts
1 site in 1 country.
About this study
In its simplest terms, obesity is the results of a positive balance between food intake and energy expenditure (EE). I.e., we take in more energy, in the form of food, than we expend, e.g., by exercise. In our sedentary society, resting EE accounts for most of total energy expenditure. The sympathetic nervous system (SNS, the one that produces adrenaline) is thought to contribute to resting EE. This conclusion is based on experiments where resting EE is decreased by beta-blockers, high blood pressure medicines that block only one aspect of the sympathetic nervous system. The investigators propose to use a different approach, by using a medication called trimethaphan that produces transient withdrawal of the autonomic nervous system. The investigators will then compare the measured resting EE before and after SNS withdraw and quantify the degree of contribution to the resting EE by the SNS and delineate differences between healthy normal, healthy obese, and patients with autonomic dysfunctions.
Read the detailed description
The rationale for this study is that even small alterations to energy metabolism can significantly change energy balance and body weight in the long term. We will test the hypothesis that the sympathetic nervous system (SNS) activity contributes to resting and thermogenic components of energy expenditure (EE).
This study is divided in four different parts: (1), (2), (3), (4).
Part (1): we will gauge the contribution of the sympathetic nervous system to resting energy expenditure, blood pressure, and determine differences between lean, obese, and patients with primary autonomic failure .
Part (2): we will determine the degree of sympathetic blockade by a gradual infusion of the ganglionic blocker trimethaphan.[Part 2 has been closed]
Part (3): we will determine the energy balance in patients with primary autonomic failure.
Part (4): we will determine the contribution of the sympathetic nervous system to lipolysis.[Part 4 has been closed]
Subjects selections*:
For part (1) and (2) we will study six groups of subjects (n = 40 for each group): patients with pure autonomic failure, patients with multiple system atrophy, healthy normal controls (BMI <= 25), obese controls (BMI 30-40) and obese hypertensive (BMI 30-40) and lean hypertensive (BMI 20-28). A time interval of at least 1 week is required for those subjects who wish to participate in part (1) and part (2). For part (3) we will study two groups of subjects (n=12 for each group): patients with autonomic failure, and their age sex-matched sedentary, healthy controls. For part (4) we will study two groups of subjects (n=12 for each group): healthy normal controls (BMI 20-25), obese controls (BMI 30-40).
*Part 2 and 4 have been closed.
- Conditions
- OBESITY, HYPERTENSION, PURE AUTONOMIC FAILURE, SHY-DRAGER SYNDROME
- Being tested
- Trimethaphan, Pseudoephedrine
- Keywords
- OBESITY, RESTING ENERGY EXPENDITURE, SYMPATHETIC NERVOUS SYSTEM, HYPERTENSION, AUTONOMIC FAILURE
- Medical subject headings
- Obesity, Hypertension, Pure Autonomic Failure, Shy-Drager Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimethaphanDrug
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 2-4 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1 hour
TrimethaphanDrug
Start dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 30 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1-2 hours
PseudoephedrineDrug
Also called Sudafed
30mg tablet,VO. Single dose.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Other | Estimation of resting energy expenditure and effect of autonomic blockade with trimethaphan infusion. Receives: Drug: Trimethaphan |
| Part 2 (closed) | Other | Estimation of autonomic function and effect of autonomic blockade with trimethaphan infusion. Receives: Drug: Trimethaphan |
| Part 3 | Other | Estimation of energy metabolism and effect of sympathetic stimulation with pseudoephedrine. Receives: Drug: Pseudoephedrine |
| Part 4a (closed) | Other | Isoproterenol sensitivity in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion. Receives: Drug: Trimethaphan |
| Part 4b (closed) | Other | Metabolic and hemodynamic response to submaximal exercise in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion. Receives: Drug: Trimethaphan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in supine systolic blood pressure after achieving complete ganglionic blockade.
Measured: 1-2 hour
Secondary outcomes (1)
Change in resting energy expenditure after achieving complete autonomic blockade.
Measured: 1-2 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startApr 2003
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OBESITYStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University Medical Center
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00179023
- Sponsor's protocol ID
- 020548
- Other IDs
- HL56693
- Status last verified
- Feb 2018
- First submitted
- 13 Sep 2005
- Last updated
- 1 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, Farley G, Paranjape SY, Davis SN, Biaggioni I. Autonomic contribution to blood pressure and metabolism in obesity. Hypertension. 2007 Jan;49(1):27-33. doi: 10.1161/01.HYP.0000251679.87348.05. Epub 2006 Nov 20.
PubMed 17116758Shibao C, Buchowski MS, Chen KY, Yu C, Biaggioni I. Chronic sympathetic attenuation and energy metabolism in autonomic failure. Hypertension. 2012 May;59(5):985-90. doi: 10.1161/HYPERTENSIONAHA.111.190157. Epub 2012 Apr 2.
PubMed 22469621
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Autonomic Nervous System and Obesity
- ClinicalTrials.gov ID
- NCT00179023
- Acronym / sponsor ID
- 020548
- Conditions
- OBESITY, HYPERTENSION, PURE AUTONOMIC FAILURE, SHY-DRAGER SYNDROME
- Keywords
- OBESITY, RESTING ENERGY EXPENDITURE, SYMPATHETIC NERVOUS SYSTEM, HYPERTENSION, AUTONOMIC FAILURE
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Apr 2003
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 15 Sep 2005 (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.
In its simplest terms, obesity is the results of a positive balance between food intake and energy expenditure (EE). I.e., we take in more energy, in the form of food, than we expend, e.g., by exercise. In our sedentary society, resting EE accounts for most of total energy expenditure. The sympathetic nervous system (SNS, the one that produces adrenaline) is thought to contribute to resting EE. This conclusion is based on experiments where resting EE is decreased by beta-blockers, high blood pressure medicines that block only one aspect of the sympathetic nervous system. The investigators propose to use a different approach, by using a medication called trimethaphan that produces transient withdrawal of the autonomic nervous system. The investigators will then compare the measured resting EE before and after SNS withdraw and quantify the degree of contribution to the resting EE by the SNS and delineate differences between healthy normal, healthy obese, and patients with autonomic dysfunctions.
Detailed description
The rationale for this study is that even small alterations to energy metabolism can significantly change energy balance and body weight in the long term. We will test the hypothesis that the sympathetic nervous system (SNS) activity contributes to resting and thermogenic components of energy expenditure (EE).
This study is divided in four different parts: (1), (2), (3), (4).
Part (1): we will gauge the contribution of the sympathetic nervous system to resting energy expenditure, blood pressure, and determine differences between lean, obese, and patients with primary autonomic failure .
Part (2): we will determine the degree of sympathetic blockade by a gradual infusion of the ganglionic blocker trimethaphan.[Part 2 has been closed]
Part (3): we will determine the energy balance in patients with primary autonomic failure.
Part (4): we will determine the contribution of the sympathetic nervous system to lipolysis.[Part 4 has been closed]
Subjects selections*:
For part (1) and (2) we will study six groups of subjects (n = 40 for each group): patients with pure autonomic failure, patients with multiple system atrophy, healthy normal controls (BMI <= 25), obese controls (BMI 30-40) and obese hypertensive (BMI 30-40) and lean hypertensive (BMI 20-28). A time interval of at least 1 week is required for those subjects who wish to participate in part (1) and part (2). For part (3) we will study two groups of subjects (n=12 for each group): patients with autonomic failure, and their age sex-matched sedentary, healthy controls. For part (4) we will study two groups of subjects (n=12 for each group): healthy normal controls (BMI 20-25), obese controls (BMI 30-40).
*Part 2 and 4 have been closed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Other | Drug: TrimethaphanEstimation of resting energy expenditure and effect of autonomic blockade with trimethaphan infusion. |
| Part 2 (closed) | Other | Drug: TrimethaphanEstimation of autonomic function and effect of autonomic blockade with trimethaphan infusion. |
| Part 3 | Other | Drug: PseudoephedrineEstimation of energy metabolism and effect of sympathetic stimulation with pseudoephedrine. |
| Part 4a (closed) | Other | Drug: TrimethaphanIsoproterenol sensitivity in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion. |
| Part 4b (closed) | Other | Drug: TrimethaphanMetabolic and hemodynamic response to submaximal exercise in adipose and muscle tissue with and without systemic autonomic blockade with trimethaphan infusion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy normal (BMI <= 25 Kg/m2), obese (BMI between 30 and 40)volunteers, lean hypertensive (BMI 20-28 Kg/m2), and obese hypertensive (BMI between 30 and 40)
- Ages 18-60
- Patients with pure autonomic failure and multiple system atrophy ages 18-80, referred to our service for the diagnosis and treatment of their condition, and their age sex-matched sedentary, healthy controls ages 18-80
Key exclusion criteria (5 listed)
- All medical students
- Pregnant women
- Heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction, glaucoma
- History of serious allergies or asthma
- Subjects using beta-blockers
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 |
|---|---|---|
| TrimethaphanStart dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 2-4 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1 hour | Drug | Part 1, Part 4a (closed), Part 4b (closed) |
| TrimethaphanStart dose: 0.05 ml/min (0.5 mg/min), IV infusion. The dose will be increased every 30 minutes to 1, 2, 4, and 5 mg/min. Total duration: 1-2 hours | Drug | Part 2 (closed) |
| PseudoephedrineAlso: Sudafed30mg tablet,VO. Single dose. | Drug | Part 3 |
Primary outcome
Change in supine systolic blood pressure after achieving complete ganglionic blockade.
Time frame: 1-2 hour
1 secondary outcome
Change in resting energy expenditure after achieving complete autonomic blockade.
Time frame: 1-2 hour
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 1 Mar 2018.
- Results publication: PubMed 17116758Shibao C, Gamboa A, Diedrich A, Ertl AC, Chen KY, Byrne DW, Farley G, Paranjape SY, Davis SN, Biaggioni I. Autonomic contribution to blood pressure and metabolism in obesity. Hypertension. 2007 Jan;49(1):27-33. doi: 10.1161/01.HYP.0000251679.87348.05. Epub 2006 Nov 20.
- Results publication: PubMed 22469621Shibao C, Buchowski MS, Chen KY, Yu C, Biaggioni I. Chronic sympathetic attenuation and energy metabolism in autonomic failure. Hypertension. 2012 May;59(5):985-90. doi: 10.1161/HYPERTENSIONAHA.111.190157. Epub 2012 Apr 2.
- 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.
Italo Biaggioni, MD principal investigator
Vanderbilt University
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 Trimethaphan and Pseudoephedrine in people with OBESITY and HYPERTENSION, run by Vanderbilt 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 3 inclusion and 5 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 1 Mar 2018. 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?
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 supine systolic blood pressure after achieving complete ganglionic blockade. (time frame: 1-2 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00179023, which also lists 2 linked publications.
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 1 Mar 2018.