DiabetesPhase 4CentrinNCT01479075
The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
A Phase 4 study testing intransal insulin and taVNS in people with Diabetes, run by German Diabetes Center at 1 site in Germany.
Trial summary
Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve. Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- intransal insulin and taVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2011to Jun 2014
- Phase
- Phase 4
- 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 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 30 and ≤ 70 years
- balanced gender ratio (50: 50)
- BMI 20-25 kg/m² (normal weight subjects)
- BMI 25-35 kg/m² (obese subjects)
Who cannot join
- acute illness within the last 2 weeks before the examination
- autoimmune diseases and disorders immune- compromised (leukocytes <5000/μl)
- renal insufficiency (creatinine> 1.5 mg / dl)
- heart disease, condition after heart attack
- anemia (Hb <12 g / l, controls at each examination), blood donation within 4 weeks before the examination
- participation in another study within 2 months before the examination
Show all 21Show fewer
- wear a metal or magnetic objects on or in the body
- claustrophobia
- use of immunomodulatory drugs (cortisol, antihistamines, aspirin)
- thyroid disease
- taking glitazones and insulin therapy
- pregnancy, lactation, menstruation
- cigarette smoking, use of alcohol or drugs, psychiatric disorders
- risk for / or manifest AIDS (HIV) or hepatitis B or C
- liver disease is not attributed to the existence of a non-alcoholic steatosis
- night shift work or circumstances, which do not allow the normal day-night rhythm
- bleeding disorders or disorders in wound healing
- hypersensitivity to local anesthetics
- malignant cancer
- heart rhythm disorders
- polyneuropathy
Trial locations and contacts
1 site in 1 country.
Germany1 site
German Diabetic Center
Düsseldorf, North Rhine-Westphalia, 40225
About this study
Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.
The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.
Read the detailed description
Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.
The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.
Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.
- Conditions
- Diabetes
- Being tested
- intransal insulin, Placebo, taVNS, sham stimulation
- Keywords
- central insulin, insulin resistance, energy metabolism
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intransal insulinDrug
Also called intranasal insulin
4x 40mU intranasal insulin
PlaceboDrug
Also called intranasal placebo spray
taVNSDevice
Also called transcutaneous auricular vagus nerve stimulation
sham stimulationDevice
Also called sham stimulation in the ear lobe
| Study group | Role | What they receive |
|---|---|---|
| intranasal insulin in patients | Experimental | intranasal insulin is applied to diabetic patients under fasting conditions Receives: Drug: intransal insulin |
| intransal insulin in study participants | Experimental | intranasal insulin is applied to healthy patients under fasting conditions Receives: Drug: intransal insulin |
| placebo in patients | Placebo comparator | placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions Receives: Drug: Placebo |
| placebo in study participants | Experimental | placebo spray is applied intranasally in healthy participants under fasting conditions Receives: Drug: Placebo |
| taNVS | Experimental | Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants Receives: Device: taVNS |
| Sham stimulation | Placebo comparator | Sham stimulation in the ear lobe is applied for 14 min in healthy participants Receives: Device: sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity
Assessment of insulin sensitivity with gold standard methods
Measured: 6 months
Secondary outcomes (1)
Energy metabolism
Energy metabolism is assessed from gold standard methods
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2011 (estimated)
- Study startAug 2011
- Primary completionJan 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Diabetes Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Roden, MD, Prof, Study director, Germyn Diabetic CenterJulia Szendrödi, MD, PhD, Principal investigator, German Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01479075
- Sponsor's protocol ID
- Centrin
- Acronym
- Centrin
- Status last verified
- Jun 2023
- First submitted
- 22 Nov 2011
- Last updated
- 5 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.
PubMed 25573069Heni M, Wagner R, Kullmann S, Veit R, Mat Husin H, Linder K, Benkendorff C, Peter A, Stefan N, Haring HU, Preissl H, Fritsche A. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014 Dec;63(12):4083-8. doi: 10.2337/db14-0477. Epub 2014 Jul 15.
PubMed 25028522Gancheva S, Koliaki C, Bierwagen A, Nowotny P, Heni M, Fritsche A, Haring HU, Szendroedi J, Roden M. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans. Diabetes. 2015 Jun;64(6):1966-75. doi: 10.2337/db14-0892. Epub 2015 Jan 9.
PubMed 25576060
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism
- ClinicalTrials.gov ID
- NCT01479075
- Acronym / sponsor ID
- Centrin / Centrin
- Conditions
- Diabetes
- Keywords
- central insulin, insulin resistance, energy metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- German Diabetes CenterUniversity, hospital or other
- Study start
- Aug 2011 (actual)
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 24 Nov 2011 (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.
Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.
The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.
Detailed description
Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.
The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.
Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| intranasal insulin in patients | Experimental | Drug: intransal insulinintranasal insulin is applied to diabetic patients under fasting conditions |
| intransal insulin in study participants | Experimental | Drug: intransal insulinintranasal insulin is applied to healthy patients under fasting conditions |
| placebo in patients | Placebo comparator | Drug: Placeboplacebo spray is applied intranasally in type 2 diabetes patients under fasting conditions |
| placebo in study participants | Experimental | Drug: Placeboplacebo spray is applied intranasally in healthy participants under fasting conditions |
| taNVS | Experimental | Device: taVNSTranscutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants |
| Sham stimulation | Placebo comparator | Device: sham stimulationSham stimulation in the ear lobe is applied for 14 min in healthy participants |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 30 and ≤ 70 years
- balanced gender ratio (50: 50)
- BMI 20-25 kg/m² (normal weight subjects)
- BMI 25-35 kg/m² (obese subjects)
Key exclusion criteria (21 listed)
- acute illness within the last 2 weeks before the examination
- autoimmune diseases and disorders immune- compromised (leukocytes <5000/μl)
- renal insufficiency (creatinine> 1.5 mg / dl)
- heart disease, condition after heart attack
- anemia (Hb <12 g / l, controls at each examination), blood donation within 4 weeks before the examination
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 |
|---|---|---|
| intransal insulinAlso: intranasal insulin4x 40mU intranasal insulin | Drug | intranasal insulin in patients, intransal insulin in study participants |
| PlaceboAlso: intranasal placebo spray | Drug | placebo in patients, placebo in study participants |
| taVNSAlso: transcutaneous auricular vagus nerve stimulation | Device | taNVS |
| sham stimulationAlso: sham stimulation in the ear lobe | Device | Sham stimulation |
Primary outcome
Insulin sensitivity
Time frame: 6 months
Assessment of insulin sensitivity with gold standard methods
1 secondary outcome
Energy metabolism
Time frame: 6 months
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 5 Jun 2023.
- Background: PubMed 25573069Frangos E, Ellrich J, Komisaruk BR. Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans. Brain Stimul. 2015 May-Jun;8(3):624-36. doi: 10.1016/j.brs.2014.11.018. Epub 2014 Dec 6.
- Background: PubMed 25028522Heni M, Wagner R, Kullmann S, Veit R, Mat Husin H, Linder K, Benkendorff C, Peter A, Stefan N, Haring HU, Preissl H, Fritsche A. Central insulin administration improves whole-body insulin sensitivity via hypothalamus and parasympathetic outputs in men. Diabetes. 2014 Dec;63(12):4083-8. doi: 10.2337/db14-0477. Epub 2014 Jul 15.
- Results publication: PubMed 25576060Gancheva S, Koliaki C, Bierwagen A, Nowotny P, Heni M, Fritsche A, Haring HU, Szendroedi J, Roden M. Effects of intranasal insulin on hepatic fat accumulation and energy metabolism in humans. Diabetes. 2015 Jun;64(6):1966-75. doi: 10.2337/db14-0892. Epub 2015 Jan 9.
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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.
Michael Roden, MD, Prof study director
Germyn Diabetic Center
Julia Szendrödi, MD, PhD principal investigator
German Diabetes Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing intransal insulin and taVNS in people with Diabetes, run by German Diabetes Center at 1 site in Germany.
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 21 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 5 Jun 2023. 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 Germany. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Insulin sensitivity (time frame: 6 months). 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 NCT01479075, which also lists 3 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 5 Jun 2023.