Diabetes Mellitus, Type 2NCT02872922
Effects of Low Intensity Therapeutic Ultrasound on Endothelial Function
A study testing Low intensity therapeutic ultrasound in people with Diabetes Mellitus, Type 2, run by Universidade Federal de Santa Maria at 1 site in Brazil.
Trial summary
Endothelium is a cell layer that interposes blood and smooth muscle of vessels. This biological sensor reacts to physical and chemical stimuli by synthesis and/or liberation of regulatory substances like nitric oxide (NO), which acts on vascular tone, growth of muscle cells and platelet aggregation and leukocyte. Read more about this study
- Who is it for?
- Ages 25 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Low intensity therapeutic ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteBrazil
- Study dates
- 10 Dec 2016to 20 Sep 2017
- Phase
- Interventional
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subjects that joined the study will be alphabetized volunteers
- Age between 25 and 65 years old,
- Absence of morbid obesity,
- Non-smokers,
- With no symptoms of skeletal muscle disorders,
- No previous performing cardiovascular surgery,
- No previous diagnose of rheumatic, neurological, oncological, immune or hematologic diseases,
- Without evidence of psychiatric diseases and/or cognitive deficit.
Who cannot join
- Insulin dependent diabetes
- Leukocytosis, impaired fasting glycemia (<70 and >300 mg/dL) and
- Brachial artery diameter less than 2.5mm and larger than 5.0mm.
- On the day of the assessments have consumed of the alcoholic drink, caffeine and citrus juice
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Universidade Federal do Rio Grande
Rio Grande, Rio Grande do Sul, 96200-190
About this study
Official title: Effects of Therapeutic Ultrasound on Endothelial Function of Patients With Type 2 Diabetes Mellitus: Randomized Clinical Trial
Endothelium is a cell layer that interposes blood and smooth muscle of vessels. This biological sensor reacts to physical and chemical stimuli by synthesis and/or liberation of regulatory substances like nitric oxide (NO), which acts on vascular tone, growth of muscle cells and platelet aggregation and leukocyte. Clinically, endothelial function measured by technique flow-mediated dilation (FMD) is a strong predictor of cardiovascular events and all-cause mortality. Previo study demonstrated that continuous and pulsed therapeutic 1-MHz ultrasound waveforms improved endothelial function in health volunteers and this vasodilation persisted for 20 min, which provided them with anti-inflammatory vascular effects. In subjects with type 2 diabetes (DM2) the chronical hyperglycemia and dyslipidemia reduce NO bioavailability causing endothelial dysfunction. Low intensity therapeutic ultrasound is an electrotherapeutic instrument employed in musculoskeletal injuries that promotes endothelium-dependent vasodilation, and its mechanism of action has not been studied on DM2. The aim of our study is evaluate endothelial function of patients with DM2 after different waveforms (placebo, continuous and pulsed) of therapeutic ultrasound. Therapeutic ultrasound is a electrotherapeutic instrument that can changes arterial endothelial function of subjects with DM2 because of NO bioavailability increasing, which implies anti-inflammatory and vasodilatory beneficial alterations for diabetic patients.
Read the detailed description
Evaluation of endothelial function will be made by flow-mediated dilation (FMD). The therapeutic ultrasound will applied over brachial artery using continuous (CUT: 0,4W/cm2), pulsed (PUT: 20% duty cycle, 0,08W/cm2SATA) and Placebo (equipment off) waveforms during 5min in 3 intercalated days.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Low intensity therapeutic ultrasound
- Keywords
- Endothelial function, Ultrasonic Therapy, Vascular endothelium, Nitric oxide, Ultrasound
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low intensity therapeutic ultrasoundOther
Also called Ultrasonic therapy, Ultrasound
The ultrasound equipment (Sonopulse III, 1 MHz, IBRAMED, Brazil) was calibrated with the radiation force method. In study, the head of the transducer will be positioned and applied for 5 min over the brachial artery at the same point that will be evaluated the endothelium function (Cruz et al., 2016). Continuous waveforms of ultrasound therapy (CWUT) are applied in the stationary mode for 5 minutes at a spatial averaged temporal intensity (SATA) of 0.4 W/cm2 using a transducer 1-MHz. A pulsed waveform of ultrasound therapy (PWUT) are applied (5 minutes) with a 20% duty cycle (2 ms on, 8 ms off), which represents a constant intensity of 0.08 W/cm2 SATA. In the placebo intervention, all of the procedures above are repeated, but with the ultrasound equipment powered off (Cruz et al., 2016).
| Study group | Role | What they receive |
|---|---|---|
| Endothelial function after CWUT | Active comparator | Endothelial function of the all patients before and after application continuous waveform of ultrasound therapy (CWUT) measured by technique flow-mediated dilation (FMD). Receives: Other: Low intensity therapeutic ultrasound |
| Endothelial function after PWUT | Active comparator | Endothelial function of the all patients before and after application pulsed waveform of ultrasound therapy (PWUT) measured by technique flow-mediated dilation (FMD). Receives: Other: Low intensity therapeutic ultrasound |
| Endothelial function after PLACEBO | Active comparator | In the placebo intervention, all of the procedures above are repeated, but with the ultrasound equipment powered off. Endothelial function of the all patients before and after application placebo waveform of ultrasound therapy measured by technique flow-mediated dilation (FMD) Receives: Other: Low intensity therapeutic ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of the endothelium-dependent vasodilation (%FMD)
Vessel diameter responses to reactive hyperemia are expressed as percentage change in relation to diameter before cuff inflation (%FMD = [(hyperemia maximum diameter - baseline precuff diameter)/(baseline precuff diameter)] / 100) (Corretti et al. 2002; Thijssen et al. 2011).
Baseline precuff diameter is expressed in millimeter (mm). Hyperemia maximum diameter is expressed in millimeter (mm). Arterial endothelium-dependent vasodilation are evaluated by technique flow-mediated dilation (FMD) with high-resolution vascular ultrasound and a 5- to 12-MHz linear transducer (Logiq P6, GE Healthcare, GE Ultrasound Korea), according to the American Heart Association Guidelines (Corretti et al. 2002), with adjustments (Thijssen et al. 2011).
Measured: Five minutes after application of therapeutic ultrasound
Secondary outcomes (1)
Percentage of the endothelium-independent vasodilation (%NMD)
Endothelium-independent vasodilation is measured after sublingual nitroglycerin (NMD) spray (0.4 mg). Vessel diameter responses nitroglycerin are expressed as percentage change in relation to diameter before cuff inflation and before drug administration (%NMD = [(nitroglycerin maximum diameter - baseline precuff diameter)/(baseline precuff diameter)] / 100) (Corretti et al. 2002; Iida et al. 2006; Thijssen et al. 2011). Baseline precuff diameter is expressed in millimeter (mm) and Nitroglycerin maximum diameter is expressed in millimeter (mm).
Measured: Five minutes after application of therapeutic ultrasound
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2016 (estimated)
- Study start10 Dec 2016
- Primary completion20 Sep 2017
- Study completion20 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidade Federal de Santa Maria
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Luis Ulisses Signori, Universidade Federal de Santa Maria
- Investigators
- Luis U Signori, PhD, Principal investigator, Universidade Federal de Santa Maria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02872922
- Sponsor's protocol ID
- UFSM1
- Status last verified
- Sep 2017
- First submitted
- 11 Aug 2016
- Last updated
- 21 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.
PubMed 11788217Poredos P, Jezovnik MK. Testing endothelial function and its clinical relevance. J Atheroscler Thromb. 2013;20(1):1-8. doi: 10.5551/jat.14340. Epub 2012 Sep 10.
PubMed 22972428Shechter M, Shechter A, Koren-Morag N, Feinberg MS, Hiersch L. Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. Am J Cardiol. 2014 Jan 1;113(1):162-7. doi: 10.1016/j.amjcard.2013.08.051. Epub 2013 Oct 5.
PubMed 24169007Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H2-12. doi: 10.1152/ajpheart.00471.2010. Epub 2010 Oct 15.
PubMed 20952670Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, Rigatto C, Komenda P, Sood MM, Tangri N. Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging. 2014 Jul;15(7):736-46. doi: 10.1093/ehjci/jet256. Epub 2014 Jan 7.
PubMed 24399339Cruz JM, Hauck M, Cardoso Pereira AP, Moraes MB, Martins CN, da Silva Paulitsch F, Plentz RD, Peres W, Vargas da Silva AM, Signori LU. Effects of Different Therapeutic Ultrasound Waveforms on Endothelial Function in Healthy Volunteers: A Randomized Clinical Trial. Ultrasound Med Biol. 2016 Feb;42(2):471-80. doi: 10.1016/j.ultrasmedbio.2015.10.002. Epub 2015 Nov 12.
PubMed 26578361
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Therapeutic Ultrasound on Endothelial Function of Patients With Type 2 Diabetes Mellitus: Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02872922
- Acronym / sponsor ID
- UFSM1
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Endothelial function, Ultrasonic Therapy, Vascular endothelium, Nitric oxide, Ultrasound
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Universidade Federal de Santa MariaUniversity, hospital or other
- Study start
- 10 Dec 2016 (actual)
- Primary completion
- 20 Sep 2017 (actual)
- Study completion
- 20 Sep 2017 (actual)
- First posted
- 19 Aug 2016 (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.
Endothelium is a cell layer that interposes blood and smooth muscle of vessels. This biological sensor reacts to physical and chemical stimuli by synthesis and/or liberation of regulatory substances like nitric oxide (NO), which acts on vascular tone, growth of muscle cells and platelet aggregation and leukocyte. Clinically, endothelial function measured by technique flow-mediated dilation (FMD) is a strong predictor of cardiovascular events and all-cause mortality. Previo study demonstrated that continuous and pulsed therapeutic 1-MHz ultrasound waveforms improved endothelial function in health volunteers and this vasodilation persisted for 20 min, which provided them with anti-inflammatory vascular effects. In subjects with type 2 diabetes (DM2) the chronical hyperglycemia and dyslipidemia reduce NO bioavailability causing endothelial dysfunction. Low intensity therapeutic ultrasound is an electrotherapeutic instrument employed in musculoskeletal injuries that promotes endothelium-dependent vasodilation, and its mechanism of action has not been studied on DM2. The aim of our study is evaluate endothelial function of patients with DM2 after different waveforms (placebo, continuous and pulsed) of therapeutic ultrasound. Therapeutic ultrasound is a electrotherapeutic instrument that can changes arterial endothelial function of subjects with DM2 because of NO bioavailability increasing, which implies anti-inflammatory and vasodilatory beneficial alterations for diabetic patients.
Detailed description
Evaluation of endothelial function will be made by flow-mediated dilation (FMD). The therapeutic ultrasound will applied over brachial artery using continuous (CUT: 0,4W/cm2), pulsed (PUT: 20% duty cycle, 0,08W/cm2SATA) and Placebo (equipment off) waveforms during 5min in 3 intercalated days.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Endothelial function after CWUT | Active comparator | Other: Low intensity therapeutic ultrasoundEndothelial function of the all patients before and after application continuous waveform of ultrasound therapy (CWUT) measured by technique flow-mediated dilation (FMD). |
| Endothelial function after PWUT | Active comparator | Other: Low intensity therapeutic ultrasoundEndothelial function of the all patients before and after application pulsed waveform of ultrasound therapy (PWUT) measured by technique flow-mediated dilation (FMD). |
| Endothelial function after PLACEBO | Active comparator | Other: Low intensity therapeutic ultrasoundIn the placebo intervention, all of the procedures above are repeated, but with the ultrasound equipment powered off. Endothelial function of the all patients before and after application placebo waveform of ultrasound therapy measured by technique flow-mediated dilation (FMD) |
Who may qualify
- Ages
- 25 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The subjects that joined the study will be alphabetized volunteers
- Age between 25 and 65 years old,
- Absence of morbid obesity,
- Non-smokers,
- With no symptoms of skeletal muscle disorders,
Key exclusion criteria (4 listed)
- Insulin dependent diabetes
- Leukocytosis, impaired fasting glycemia (<70 and >300 mg/dL) and
- Brachial artery diameter less than 2.5mm and larger than 5.0mm.
- On the day of the assessments have consumed of the alcoholic drink, caffeine and citrus juice
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 |
|---|---|---|
| Low intensity therapeutic ultrasoundAlso: Ultrasonic therapy, UltrasoundThe ultrasound equipment (Sonopulse III, 1 MHz, IBRAMED, Brazil) was calibrated with the radiation force method. In study, the head of the transducer will be positioned and applied for 5 min over the brachial artery at the same point that will be evaluated the endothelium function (Cruz et al., 2016). Continuous waveforms of ultrasound therapy (CWUT) are applied in the stationary mode for 5 minutes at a spatial averaged temporal intensity (SATA) of 0.4 W/cm2 using a transducer 1-MHz. A pulsed waveform of ultrasound therapy (PWUT) are applied (5 minutes) with a 20% duty cycle (2 ms on, 8 ms off), which represents a constant intensity of 0.08 W/cm2 SATA. In the placebo intervention, all of the procedures above are repeated, but with the ultrasound equipment powered off (Cruz et al., 2016). | Other | Endothelial function after CWUT, Endothelial function after PLACEBO, Endothelial function after PWUT |
Primary outcome
Percentage of the endothelium-dependent vasodilation (%FMD)
Time frame: Five minutes after application of therapeutic ultrasound
Vessel diameter responses to reactive hyperemia are expressed as percentage change in relation to diameter before cuff inflation (%FMD = [(hyperemia maximum diameter - baseline precuff diameter)/(baseline precuff diameter)] / 100) (Corretti et al. 2002; Thijssen et al. 2011). Baseline precuff diameter is expressed in millimeter (mm). Hyperemia maximum diameter is expressed in millimeter (mm). Arterial endothelium-dependent vasodilation are evaluated by technique flow-mediated dilation (FMD) with high-resolution vascular ultrasound and a 5- to 12-MHz linear transducer (Logiq P6, GE Healthcare, GE Ultrasound Korea), according to the American Heart Association Guidelines (Corretti et al. 2002), with adjustments (Thijssen et al. 2011).
1 secondary outcome
Percentage of the endothelium-independent vasodilation (%NMD)
Time frame: Five minutes after application of therapeutic ultrasound
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 21 Sep 2017.
- Background: PubMed 11788217Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R; International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002 Jan 16;39(2):257-65. doi: 10.1016/s0735-1097(01)01746-6.
- Background: PubMed 22972428Poredos P, Jezovnik MK. Testing endothelial function and its clinical relevance. J Atheroscler Thromb. 2013;20(1):1-8. doi: 10.5551/jat.14340. Epub 2012 Sep 10.
- Background: PubMed 24169007Shechter M, Shechter A, Koren-Morag N, Feinberg MS, Hiersch L. Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. Am J Cardiol. 2014 Jan 1;113(1):162-7. doi: 10.1016/j.amjcard.2013.08.051. Epub 2013 Oct 5.
- Background: PubMed 20952670Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011 Jan;300(1):H2-12. doi: 10.1152/ajpheart.00471.2010. Epub 2010 Oct 15.
- Background: PubMed 24399339Xu Y, Arora RC, Hiebert BM, Lerner B, Szwajcer A, McDonald K, Rigatto C, Komenda P, Sood MM, Tangri N. Non-invasive endothelial function testing and the risk of adverse outcomes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging. 2014 Jul;15(7):736-46. doi: 10.1093/ehjci/jet256. Epub 2014 Jan 7.
- Results publication: PubMed 26578361Cruz JM, Hauck M, Cardoso Pereira AP, Moraes MB, Martins CN, da Silva Paulitsch F, Plentz RD, Peres W, Vargas da Silva AM, Signori LU. Effects of Different Therapeutic Ultrasound Waveforms on Endothelial Function in Healthy Volunteers: A Randomized Clinical Trial. Ultrasound Med Biol. 2016 Feb;42(2):471-80. doi: 10.1016/j.ultrasmedbio.2015.10.002. Epub 2015 Nov 12.
- 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.
Luis U Signori, PhD principal investigator
Universidade Federal de Santa Maria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low intensity therapeutic ultrasound in people with Diabetes Mellitus, Type 2, run by Universidade Federal de Santa Maria at 1 site in Brazil.
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 8 inclusion and 4 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 21 Sep 2017. 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 Brazil. 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?
Percentage of the endothelium-dependent vasodilation (%FMD) (time frame: Five minutes after application of therapeutic ultrasound). 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 NCT02872922, which also lists 6 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 21 Sep 2017.