ObesityPhase 1/2RDVCGHNCT02365285
Racial Differences in Vagal Control of Glucose Homeostasis
A Phase 1/2 study testing Galantamine, Intralipid and Heparin in people with Obesity, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Galantamine, Intralipid and Heparin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to 5 Oct 2017
- Phase
- Phase 1/2
- 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 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Female
- African American or white (race will be self-defined, but only subjects who report both parents of the same race will be included)
- 18-60 years old
- BMI 30-45 Kg/m2
- Not pregnant or breastfeeding
Who cannot join
- Pregnant or breastfeeding
- Diabetes diagnosis (defined by the American Diabetes Association (ADA) criteria)38
- Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy.
- Arrhythmia (first-, second-, and third-degree atrioventricular (AV) block)
- Significant weight change >5% in the past 3 months
- Impaired hepatic function (AST and/or Alanine transaminase (ALT) > one and one half times (1.5X) upper limit of normal range)
Show all 12Show fewer
- Impaired renal function (eGFR <60ml/min)
- Users of strong inhibitors of Cytochrome P450 3A4 (CYP3A4) or cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6)
- Users of other acetylcholinesterase inhibitors such as pyridostigmine or bethanechol
- History of alcohol or drug abuse
- Mental conditions rendering the subject unable to understand the nature, scope, and possible consequences of the study
- Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.
Read the detailed description
Obesity has a greater detrimental impact on the health of African American women (AAW) than on any other racial or gender group. Nearly 80% of AAW are overweight or obese. Reduced insulin sensitivity is more prevalent among AAW as compared to white women and men of both races. This condition puts AAW at increased risk for the development of type 2 diabetes mellitus. The exact mechanism underlying these pathophysiological differences remains unknown. The investigators have found that obese AAW have decreased parasympathetic nerve (PNS) activity compared to whites and recent studies in animal models showed that the PNS confers protection against oxidative stress. In our AA cohort, PNS activity was directly correlated with insulin sensitivity in obese AAW even after controlling for differences in age, blood pressure and visceral adiposity. Equally important, the investigators also showed that the decrease in insulin sensitivity was associated with increased oxidative stress as measured by plasma levels of F2-isoprostanes. Taken together these findings lead us to hypothesize that the decreased PNS activity in obese AAW compared to white women has deleterious effects on oxidative stress and insulin sensitivity.The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.
- Conditions
- Obesity
- Being tested
- Galantamine, Placebo Oral Capsule, Intralipid, Heparin
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GalantamineDrug
Also called Razadyne
16 mg po prior to the infusion of intralipid
Placebo Oral CapsuleDrug
Placebo oral capsule prior to the infusion of intralipid/heparin
IntralipidDrug
Also called I.V. Fat Emulsion
Intralipid 20% will be infused at 0.8 mL/m2/min for 4h after oral placebo or Galantamine
HeparinDrug
heparin bolus of 1000 U will be followed by 200 U/h infusion for 4h after oral placebo or Galantamine
| Study group | Role | What they receive |
|---|---|---|
| Galantamine 16 mg then placebo | Experimental | Galantamine 16 mg po one time dose then placebo on 2nd visit Receives: Drug: Galantamine; Drug: Placebo Oral Capsule; Drug: Intralipid; Drug: Heparin |
| Placebo then Galantamine 16 mg | Placebo comparator | Placebo capsule po one time dose then Galantamine 16 mg on 2nd visit Receives: Drug: Galantamine; Drug: Placebo Oral Capsule; Drug: Intralipid; Drug: Heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Oxidative Stress: Baseline to 2 Hours
Measure F-2 isoprostanes as a marker of oxidation
Measured: Baseline to 2 hours
Change in Oxidative Stress: Baseline to 4 Hours
Measure F-2 isoprostanes as a marker of oxidation
Measured: Baseline to 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2015 (estimated)
- Study startMar 2015
- Primary completion5 Oct 2017
- Study completion5 Oct 2017
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Doris Duke Charitable Foundation
- Responsible party
- Principal investigator, Cyndya Shibao, Vanderbilt University
- Investigators
- Cyndya Shibao, MD, Principal investigator, Vanderbilt University Medical Center, Clinical Pharmacology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02365285
- Sponsor's protocol ID
- 141552
- Acronym
- RDVCGH
- Status last verified
- Feb 2019
- First submitted
- 28 Jan 2015
- Last updated
- 19 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Parsa D, Aden LA, Pitzer A, Ding T, Yu C, Diedrich A, Milne GL, Kirabo A, Shibao CA. Enhanced parasympathetic cholinergic activity with galantamine inhibited lipid-induced oxidative stress in obese African Americans. Mol Med. 2022 Jun 3;28(1):60. doi: 10.1186/s10020-022-00486-5.
PubMed 35659521
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Racial Differences in Vagal Control of Glucose Homeostasis
- ClinicalTrials.gov ID
- NCT02365285
- Acronym / sponsor ID
- RDVCGH / 141552
- Conditions
- Obesity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Doris Duke Charitable Foundation
- Study start
- Mar 2015 (actual)
- Primary completion
- 5 Oct 2017 (actual)
- Study completion
- 5 Oct 2017 (actual)
- First posted
- 18 Feb 2015 (estimated)
- Results
- Posted 19 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.
Detailed description
Obesity has a greater detrimental impact on the health of African American women (AAW) than on any other racial or gender group. Nearly 80% of AAW are overweight or obese. Reduced insulin sensitivity is more prevalent among AAW as compared to white women and men of both races. This condition puts AAW at increased risk for the development of type 2 diabetes mellitus. The exact mechanism underlying these pathophysiological differences remains unknown. The investigators have found that obese AAW have decreased parasympathetic nerve (PNS) activity compared to whites and recent studies in animal models showed that the PNS confers protection against oxidative stress. In our AA cohort, PNS activity was directly correlated with insulin sensitivity in obese AAW even after controlling for differences in age, blood pressure and visceral adiposity. Equally important, the investigators also showed that the decrease in insulin sensitivity was associated with increased oxidative stress as measured by plasma levels of F2-isoprostanes. Taken together these findings lead us to hypothesize that the decreased PNS activity in obese AAW compared to white women has deleterious effects on oxidative stress and insulin sensitivity.The investigators will test the hypothesis that acute central acetylcholinesterase inhibition will restore PNS activity and reduce oxidation in AAW compared to whites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Galantamine 16 mg then placebo | Experimental | Drug: Galantamine, Drug: Placebo Oral Capsule, Drug: Intralipid, Drug: HeparinGalantamine 16 mg po one time dose then placebo on 2nd visit |
| Placebo then Galantamine 16 mg | Placebo comparator | Drug: Galantamine, Drug: Placebo Oral Capsule, Drug: Intralipid, Drug: HeparinPlacebo capsule po one time dose then Galantamine 16 mg on 2nd visit |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Female
- African American or white (race will be self-defined, but only subjects who report both parents of the same race will be included)
- 18-60 years old
- BMI 30-45 Kg/m2
- Not pregnant or breastfeeding
Key exclusion criteria (12 listed)
- Pregnant or breastfeeding
- Diabetes diagnosis (defined by the American Diabetes Association (ADA) criteria)38
- Cardiovascular disease such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy.
- Arrhythmia (first-, second-, and third-degree atrioventricular (AV) block)
- Significant weight change >5% in the past 3 months
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 |
|---|---|---|
| GalantamineAlso: Razadyne16 mg po prior to the infusion of intralipid | Drug | Galantamine 16 mg then placebo, Placebo then Galantamine 16 mg |
| Placebo Oral CapsulePlacebo oral capsule prior to the infusion of intralipid/heparin | Drug | Galantamine 16 mg then placebo, Placebo then Galantamine 16 mg |
| IntralipidAlso: I.V. Fat EmulsionIntralipid 20% will be infused at 0.8 mL/m2/min for 4h after oral placebo or Galantamine | Drug | Galantamine 16 mg then placebo, Placebo then Galantamine 16 mg |
| Heparinheparin bolus of 1000 U will be followed by 200 U/h infusion for 4h after oral placebo or Galantamine | Drug | Galantamine 16 mg then placebo, Placebo then Galantamine 16 mg |
Primary outcome
Change in Oxidative Stress: Baseline to 2 Hours
Time frame: Baseline to 2 hours
Measure F-2 isoprostanes as a marker of oxidation
Change in Oxidative Stress: Baseline to 4 Hours
Time frame: Baseline to 4 hours
Measure F-2 isoprostanes as a marker of oxidation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35659521Parsa D, Aden LA, Pitzer A, Ding T, Yu C, Diedrich A, Milne GL, Kirabo A, Shibao CA. Enhanced parasympathetic cholinergic activity with galantamine inhibited lipid-induced oxidative stress in obese African Americans. Mol Med. 2022 Jun 3;28(1):60. doi: 10.1186/s10020-022-00486-5.
- 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.
Cyndya Shibao, MD principal investigator
Vanderbilt University Medical Center, Clinical Pharmacology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Galantamine, Intralipid and Heparin in people with Obesity, run by Vanderbilt University Medical Center 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 5 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: finished, as of the sponsor's last update on 19 Mar 2019. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Mar 2019). 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?
Change in Oxidative Stress: Baseline to 2 Hours (time frame: Baseline to 2 hours). 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?
On the ClinicalTrials.gov record for NCT02365285, which also lists 1 linked publication.
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 19 Mar 2019.