Normal Tension GlaucomaANSNCT01192061
Autonomic Nervous System Activity and Normal Tension Glaucoma
An observational study of Normal Tension Glaucoma, run by Military Institute od Medicine National Research Institute at 1 site in Poland.
Trial summary
Evidence has accumulated that systemic and ocular mechanisms, responsible for regulating blood flow in the area of the optic disc, such as reduced ocular perfusion pressure, abnormal autoregulation and vascular dysregulation may be involved in the pathogenesis of normal tension glaucoma (NTG). Read more about this study
- Who is it for?
- Ages 30 years and olderHealthy volunteers can take part
- Conditions the study is for
- Normal Tension Glaucoma
- How many people
- 97 participants
- Where
- 1 sitePoland
- Study dates
- Feb 2010to Jan 2011
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: NTG group: out-patient clinic of the Ophthalmology Department of the Military Medical Institute (MMI), control group: hospital stuff, family and friends of hospital stuff and patients
Who may be able to join
- NTG group
- both gender
- early to moderate NTG
- without significant cardiac or pulmonary conditions. Glaucoma is diagnosed on the basis of a glaucomatous appearance of the optic disc (cup-to-disc ratio greater than 0.6 or an interocular cup-to-disc ratio asymmetry greater than or equal to 0.2, and at least one of the following abnormalities: thinning of the rim, notching, nerve fiber layer defects, or peripapillary atrophy), correlating with visual field defects in two consecutive central 24-2 program of Humphrey threshold perimetry, according to the European Glaucoma Society (EGS) diagnostic criteria (abnormal glaucoma hemifield test or cluster of three non-edge contiguous points at the <5% level on the pattern deviation plot with at least one point at the <1% level, with < 25% fixation losses and false positives and false negatives responses). Early and moderately glaucomatous loss is defined according to the Hodapp et al. classification, based on the Mean Defect (MD) index of visual fields less than - 6 dB (decibels) and - 12 dB but more than -6 dB, respectively, and on the basis of a vertical cup/disc ratio less than 0.8.
- Control group
- both gender
Show all 9Show fewer
- age and gender-matched
- without glaucoma
- without significant cardiac or pulmonary conditions.
Who cannot join
- ocular hypertension
- primary open angle glaucoma (high pressure glaucoma, IOP>21mmHg)
- secondary open angle glaucoma
- angle closure glaucoma
- history of eye surgery
- history of eye trauma
Show all 24Show fewer
- myopia above -6.0 diopters (D)
- corneal dystrophies
- uncontrolled arterial hypertension
- atrial fibrillation
- atrial flutter
- pacemaker
- history of cardiac arrest
- vasovagal syndrome
- diabetes mellitus
- primary damage to the autonomic nervous system
- Shy-Drager syndrome
- encephalomyelitis, multiple sclerosis
- brain and spinal cord tumors
- renal failure
- carotid sinus hypersensitivity syndrome carotid sinus
- carotid artery stenosis
- pregnancy
- breast-feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Autonomic Nervous System Activity, Peripheral Microcirculation and Retrobulbar Hemodynamics in Normal Tension Glaucoma Patients.
Evidence has accumulated that systemic and ocular mechanisms, responsible for regulating blood flow in the area of the optic disc, such as reduced ocular perfusion pressure, abnormal autoregulation and vascular dysregulation may be involved in the pathogenesis of normal tension glaucoma (NTG). Defective cardiovascular neuroregulation has been advocated as a possible one of the main systemic contributing factors in the etiology of NTG. Based on the results of previous studies, the hypothesis has been posed that patients with NTG have an impaired diurnal heart rate variability (HRV) or high activity of the sympathetic component of autonomic nervous system (ANS) and endothelial dysfunction. Impaired balance of ANS, resulting in increased demand for oxygen in the tissues and subsequent low threshold of hypoxia in all organs (including the eye) can be an important link in the pathogenetic pathway of NTG, making the optic nerve more sensitive to small and short-term changes in perfusion pressure and prone to damage even under a statistically "normal" intraocular pressure (IOP).
The aim of this study is to evaluate the activity and characteristics of the following systems: the central ANS (through a 24-hour analysis of heart rate variability and blood pressure), peripheral vascular system (through the analysis of the post-occlusive hyperemia reaction within the distal part of left upper limb) and the local retrobulbar circulation as measured by color Doppler imaging (CDI) in patients with NTG and healthy volunteers. The correlations between all above systems, as well as between them and the structural and functional parameters of the optic nerve, and the retina in both groups will be also analyzed.
Read the detailed description
Fifty patients with NTG and 50 age and gender-matched control subjects will be recruited. All patients will be underwent eye examination (medical history, best corrected visual acuity, slit-lamp and stereo optic disc evaluation, Goldmann applanation tonometry, central corneal thickness measurement , Humphrey central 24-2 threshold perimetry test and optical coherence tomography of the optic nerve head, retinal nerve fibre layer and macula. CDI examination of the retrobulbar vessels will be performed. 24-hour ambulatory electrocardiogram and blood pressure monitoring will be performed simultaneously. Time- and frequency-domain measures of HRV will be calculated. BP will be measured in 20 minutes intervals during the day and 30 minutes intervals at night. The occlusive provocative test and finger hyperemia will be assessed by two-channels laser-Doppler flowmeter.
- Conditions
- Normal Tension Glaucoma
- Keywords
- autonomic nervous system, heart rate variability, blood pressure variability, retrobulbar hemodynamics, vascular dysregulation
- Medical subject headings
- Low Tension Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Normal tension glaucoma group | Not described | |
| Control group | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time and spectral-domain measures of heart rate variability
standard deviation of normal to normal RR intervals (SDNN), standard deviation of normal to normal RR intervals index (SD SD), root mean square of succesive differences (RMS-SD), percentage of normal to normal RR interval, greater than 50 ms (pNN50), low-frequency component (LF), high frequency component (HF), LF/HF) ratio
Measured: baseline
Secondary outcomes (7)
retrobulbar hemodynamic parameters of ophthalmic (OA), central retinal (CRA) and short ciliary posterior arteries (SCPA)
peak systolic velocity (PSV) of OA, CRA and SPCA, end diastolic velocity (EDV) of OA, CRA and SPCA, resistance index (RI) of OA, CRA and SPCA
Measured: baseline
measures of blood pressure (BP) diurnal variability
standard devation of of the average systolic BP (SD SBP24), diastolic BP (SD DBP24) and mean BP (SD MBP24) during the whole day, standard devation of of the average systolic BP (SD SBPd), diastolic BP (SD DBPd) and mean BP (SD MBPd) during the day and standard devation of of the average systolic BP (SD SBPn), diastolic BP (SD DBPn) and mean BP (SD MBPn) at night.
Measured: baseline
parameters of postocclusive hyperemia response
biological zero (BZ) (mean flow signal during occlusion), maximum hyperemia response (MAX) (maximum flow signal of post-occlusive hyperemia response), time of recovery (TR) (time from the end of occlusion until the moment when flow signal returns to the rest values), time to peak-flow (TM) (time from the moment of the end of occlusion until the moment of maximum hyperemic response), and half time of hyperemia (TH) (time from the moment of the end of occlusion until the moment when flow signal reaching the maximum value will fall by half)
Measured: baseline
optical coherence tomography parameters of optic nerve head
disc area (DA), cup area (CA), rim area (RA), cup/disc area ratio (CDR), cup/disc horizontal ratio (CDHR), cup/disc vertical ratio (CDVR)
Measured: baseline
optical coherence tomography parameters of the retinal nerve fibre layer (RNFL)
mean RNFL thickness (RNFL M), mean inferior RNFL thickness (RNFL I), mean superior RNFL thickness (RNFL S), mean temporal RNFL thickness (RNFL T), mean nasal RNFL thickness (RNFL N).
Measured: baseline
optical coherence tomography parameters of macula
minimum macula thickness (TF MIN), mean macula thickness (TF M), mean inferior interior macula thickness (IIM), mean superior interior macula thickness (SIM), mean nasal interior macula thickness (NIM), mean temperal interior macula thickness (TIM), mean inferior outer macula thickness (IOM), mean superior outer macula thickness (SOM), mean nasal outer macula thickness (NOM), mean temporal outer macula thickness (TOM), volume foveola (VF) and volume macula (VM).
Measured: baseline
Parameters of visual field examination
mean defect (MD), pattern standard deviation (PSD)
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2010 (estimated)
- Study startFeb 2010
- Primary completionJan 2011
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Normal Tension GlaucomaStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- Military Institute od Medicine National Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Polish Academy of Sciences, Indiana University, Medical University of Warsaw
- Investigators
- Joanna Wierzbowska, MD, PhD, Principal investigator, Military Medical Institute, Department of Ophthalmology, 128 Szaserow Str. 04-141 Warsaw, Poland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01192061
- Sponsor's protocol ID
- N N402 165637
- Acronym
- ANS
- Status last verified
- Jan 2011
- First submitted
- 30 Aug 2010
- Last updated
- 25 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Wierzbowska J, Wierzbowski R, Stankiewicz A, Robaszkiewicz J. [Autonomic nervous system and primary open angle glaucoma--pathogenetic and clinical correlations]. Klin Oczna. 2009;111(1-3):75-9. Polish.
PubMed 19517852Brown CM, Dutsch M, Michelson G, Neundorfer B, Hilz MJ. Impaired cardiovascular responses to baroreflex stimulation in open-angle and normal-pressure glaucoma. Clin Sci (Lond). 2002 Jun;102(6):623-30.
PubMed 12049615Riccadonna M, Covi G, Pancera P, Presciuttini B, Babighian S, Perfetti S, Bonomi L, Lechi A. Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma. J Glaucoma. 2003 Apr;12(2):156-63. doi: 10.1097/00061198-200304000-00011.
PubMed 12671471Kashiwagi K, Tsumura T, Ishii H, Ijiri H, Tamura K, Tsukahara S. Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography. J Glaucoma. 2000 Jun;9(3):239-46. doi: 10.1097/00061198-200006000-00007.
PubMed 10877375
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autonomic Nervous System Activity, Peripheral Microcirculation and Retrobulbar Hemodynamics in Normal Tension Glaucoma Patients.
- ClinicalTrials.gov ID
- NCT01192061
- Acronym / sponsor ID
- ANS / N N402 165637
- Conditions
- Normal Tension Glaucoma
- Keywords
- autonomic nervous system, heart rate variability, blood pressure variability, retrobulbar hemodynamics, vascular dysregulation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- Military Institute od Medicine National Research InstituteUniversity, hospital or other
- Collaborators
- Polish Academy of Sciences, Indiana University, Medical University of Warsaw
- Study start
- Feb 2010
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 31 Aug 2010 (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.
Evidence has accumulated that systemic and ocular mechanisms, responsible for regulating blood flow in the area of the optic disc, such as reduced ocular perfusion pressure, abnormal autoregulation and vascular dysregulation may be involved in the pathogenesis of normal tension glaucoma (NTG). Defective cardiovascular neuroregulation has been advocated as a possible one of the main systemic contributing factors in the etiology of NTG. Based on the results of previous studies, the hypothesis has been posed that patients with NTG have an impaired diurnal heart rate variability (HRV) or high activity of the sympathetic component of autonomic nervous system (ANS) and endothelial dysfunction. Impaired balance of ANS, resulting in increased demand for oxygen in the tissues and subsequent low threshold of hypoxia in all organs (including the eye) can be an important link in the pathogenetic pathway of NTG, making the optic nerve more sensitive to small and short-term changes in perfusion pressure and prone to damage even under a statistically "normal" intraocular pressure (IOP).
The aim of this study is to evaluate the activity and characteristics of the following systems: the central ANS (through a 24-hour analysis of heart rate variability and blood pressure), peripheral vascular system (through the analysis of the post-occlusive hyperemia reaction within the distal part of left upper limb) and the local retrobulbar circulation as measured by color Doppler imaging (CDI) in patients with NTG and healthy volunteers. The correlations between all above systems, as well as between them and the structural and functional parameters of the optic nerve, and the retina in both groups will be also analyzed.
Detailed description
Fifty patients with NTG and 50 age and gender-matched control subjects will be recruited. All patients will be underwent eye examination (medical history, best corrected visual acuity, slit-lamp and stereo optic disc evaluation, Goldmann applanation tonometry, central corneal thickness measurement , Humphrey central 24-2 threshold perimetry test and optical coherence tomography of the optic nerve head, retinal nerve fibre layer and macula. CDI examination of the retrobulbar vessels will be performed. 24-hour ambulatory electrocardiogram and blood pressure monitoring will be performed simultaneously. Time- and frequency-domain measures of HRV will be calculated. BP will be measured in 20 minutes intervals during the day and 30 minutes intervals at night. The occlusive provocative test and finger hyperemia will be assessed by two-channels laser-Doppler flowmeter.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal tension glaucoma group | – | – |
| Control group | – | – |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- NTG group: out-patient clinic of the Ophthalmology Department of the Military Medical Institute (MMI), control group: hospital stuff, family and friends of hospital stuff and patients
Key inclusion criteria (9 listed)
- NTG group
- both gender
- early to moderate NTG
- without significant cardiac or pulmonary conditions. Glaucoma is diagnosed on the basis of a glaucomatous appearance of the optic disc (cup-to-disc ratio greater than 0.6 or an interocular cup-to-disc ratio asymmetry greater than or equal to 0.2, and at least one of the following abnormalities: thinning of the rim, notching, nerve fiber layer defects, or peripapillary atrophy), correlating with visual field defects in two consecutive central 24-2 program of Humphrey threshold perimetry, according to the European Glaucoma Society (EGS) diagnostic criteria (abnormal glaucoma hemifield test or cluster of three non-edge contiguous points at the <5% level on the pattern deviation plot with at least one point at the <1% level, with < 25% fixation losses and false positives and false negatives responses). Early and moderately glaucomatous loss is defined according to the Hodapp et al. classification, based on the Mean Defect (MD) index of visual fields less than - 6 dB (decibels) and - 12 dB but more than -6 dB, respectively, and on the basis of a vertical cup/disc ratio less than 0.8.
- Control group
Key exclusion criteria (24 listed)
- ocular hypertension
- primary open angle glaucoma (high pressure glaucoma, IOP>21mmHg)
- secondary open angle glaucoma
- angle closure glaucoma
- history of eye surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Time and spectral-domain measures of heart rate variability
Time frame: baseline
standard deviation of normal to normal RR intervals (SDNN), standard deviation of normal to normal RR intervals index (SD SD), root mean square of succesive differences (RMS-SD), percentage of normal to normal RR interval, greater than 50 ms (pNN50), low-frequency component (LF), high frequency component (HF), LF/HF) ratio
7 secondary outcomes
retrobulbar hemodynamic parameters of ophthalmic (OA), central retinal (CRA) and short ciliary posterior arteries (SCPA)
Time frame: baseline
measures of blood pressure (BP) diurnal variability
Time frame: baseline
parameters of postocclusive hyperemia response
Time frame: baseline
optical coherence tomography parameters of optic nerve head
Time frame: baseline
optical coherence tomography parameters of the retinal nerve fibre layer (RNFL)
Time frame: baseline
optical coherence tomography parameters of macula
Time frame: baseline
Parameters of visual field examination
Time frame: baseline
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 25 Jan 2011.
- Background: PubMed 19517852Wierzbowska J, Wierzbowski R, Stankiewicz A, Robaszkiewicz J. [Autonomic nervous system and primary open angle glaucoma--pathogenetic and clinical correlations]. Klin Oczna. 2009;111(1-3):75-9. Polish.
- Background: PubMed 12049615Brown CM, Dutsch M, Michelson G, Neundorfer B, Hilz MJ. Impaired cardiovascular responses to baroreflex stimulation in open-angle and normal-pressure glaucoma. Clin Sci (Lond). 2002 Jun;102(6):623-30.
- Background: PubMed 12671471Riccadonna M, Covi G, Pancera P, Presciuttini B, Babighian S, Perfetti S, Bonomi L, Lechi A. Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma. J Glaucoma. 2003 Apr;12(2):156-63. doi: 10.1097/00061198-200304000-00011.
- Background: PubMed 10877375Kashiwagi K, Tsumura T, Ishii H, Ijiri H, Tamura K, Tsukahara S. Circadian rhythm of autonomic nervous function in patients with normal-tension glaucoma compared with normal subjects using ambulatory electrocardiography. J Glaucoma. 2000 Jun;9(3):239-46. doi: 10.1097/00061198-200006000-00007.
Related trials for Normal Tension Glaucoma
Enrolling by invitationPhase 1/2
Topical Insulin for Glaucoma (TING2)
Open Angle Glaucoma, Primary Open Angle Glaucoma
RecruitingObservational study
Dresden Glaucoma and Treatment Study (DGTS)
Glaucoma, Glaucoma, Open-Angle
Active, not recruitingPhase 2
Single-site Pilot Study Evaluating the Effect of QLS-111 Ophthalmic Solution on Posterior Perfusion and Vessel Dilation
Non-proliferative Diabetic Retinopathy (NPDR), Open-angle Glaucoma (OAG)
Active, not recruiting
Direct Selective Laser Trabeculoplasty in Ethnic Chinese Population
Primary Open Angle Glaucoma, Ocular Hypertension
Recruiting
Transcorneal Electrical Stimulation for the Treatment of Visual Field Defects in Patients With Open-Angle Glaucoma
Glaucoma, Primary Open Angle Glaucoma
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.
Joanna Wierzbowska, MD, PhD principal investigator
Military Medical Institute, Department of Ophthalmology, 128 Szaserow Str. 04-141 Warsaw, Poland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Tension Glaucoma, run by Military Institute od Medicine National Research Institute at 1 site in Poland.
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 9 inclusion and 24 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 25 Jan 2011. 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 Poland. 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?
Time and spectral-domain measures of heart rate variability (time frame: baseline). 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 NCT01192061, which also lists 4 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 25 Jan 2011.