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Quantification of Rising the Osmotic Pressure in Diabetic Intraretinal Fluid Accumulation (Diabetic Macular Oedema)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Birgit Sander, Glostrup University Hospital, Copenhagen
ClinicalTrials.gov Identifier:
NCT00333671
First received: June 2, 2006
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

Diabetic macular oedema is characterized by fluid accumulation in the retinal tissue from leaking retinal vessels, the capillaries. This state can lead to severe visual loss and blindness. According to basic physiologic rules several factors influence the fluid transport between the capillaries and the surrounding tissue. One of these factors is the balance between the large molecules within the vessel lumen and the retinal tissue. Some drugs change this balance, the osmotic balance, by moving the fluid from the tissue to the vessel lumen. In relation to diabetic macular oedema, treatment with such a drug potentially would reduce the retinal thickness because it extracts fluid from the retinal tissue. Glycerol has this potential. If reduction of the thickness with glycerol is confirmed, then it proves the significance of the osmotic balance in the basic nature of diabetic macular oedema.

In this study we therefore examine the time dependent change in retinal thickness after glycerol intake by an instrument called optical coherence tomography (OCT). The participants drink glycerol and the thickness of the retina is then monitored closely by OCT during the following three hours. Since diabetic changes in the retina are focal pr. definition, the secondary purpose of the study is to find any regional differences in the response. The examinations are repeated at a second visit where the patient drink another dose of glycerol, because we also want to analyse for a dose dependent response. Which dose is given at each visit is randomised on beforehand. In addition to measuring the retinal thickness a variety of examinations are performed both before and during the study, e.g. blood samples and systemic blood pressure measurements.


Condition Intervention
Diabetic Macular Oedema
Drug: Glycerol

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Diabetic Macular Oedema: the Retinal Thickness as a Function of Changes in Plasma Osmolality Evaluated by OCT.

Resource links provided by NLM:


Further study details as provided by Glostrup University Hospital, Copenhagen:

Primary Outcome Measures:
  • Retinal thickness by fast retinal thickness mapping by optical coherence tomography at times 0, 2, 4, 8, 10, 15, 20, 30, 60, 90, 120 and 180 minutes after the last swallow of glycerol.

Secondary Outcome Measures:
  • Regional differences in response by fast retinal thickness mapping by optical coherence tomography at times 0, 2, 4, 8, 10, 15, 20, 30, 60, 90, 120 and 180 minutes after the last swallow of glycerol
  • dose dependent differences in the same time spectrum.

Enrollment: 15
Study Start Date: December 2004
Study Completion Date: April 2007
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Detailed Description:

In general, when oedema is present, increasing the osmotic pressure in the retinal capillaries by an osmotic drug induces transcapillary fluid transport from the retinal tissue to the vascular lumen, according to the Starling equation. Theoretically, in diabetic macular oedema the event would lead to reduction of the retinal thickness, which could then be visualised by Optical Coherence Tomography. The main purpose of this trial is therefore to evaluate and quantify the changes in retinal thickness of the oedema after increasing the intracapillary osmotic pressure with glycerol ingestion. A reduction of the retinal thickness will confirm the application of the Starling osmotic forces on diabetic macular oedema. Secondly, we want to describe any regional differences in the retinal response and analyse for dose dependent variations.

Principles of material and methods: A prospective, randomized, clinical trial on 15 patients with diabetic significant macular oedema. At baseline the patients undergo a thorough ophthalmologic examination including ETDRS visual acuity, slit lamp biomicroscopy, Optical Coherence Tomography (Stratus-OCT), 7-field fundus photography followed by fluorescein angiography. In addition the systemic blood pressure is measured and blood samples are taken to rule out severe renal insufficiency and to estimate glycosylated haemoglobin.

The patients are all randomised to drink either 1.5 or 3 mL glycerol/kg body weight (max. 250 mL pr day) on the first of two visit dates. The last dose is given at the second visit. In the following three hours the retinal thickness is then monitored closely by Stratus-OCT after the glycerol ingestion.

The plasma osmolality and plasma triglyceride (an indirect indicator of glycerol) are confirmed by venous blood samples, also at predetermined times after the last swallow of glycerol. In addition the systemic blood pressure and the capillary blood glucose are monitored closely during the visit.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetic significant macular oedema (by biomicroscopy or OCT)
  • Visual acuity of minimum 60 letters by the ETDRS chart (4 m distance)
  • ETDRS grade between 35 and 53, both stages included
  • baseline blood pressure of max. 160/90 mmHg
  • informed consent

Exclusion Criteria:

  • another macular disease than diabetic macular oedema to explain the symptoms, incl. prior laser photocoagulation
  • pregnancy
  • moderate to severe heart or lung disease (crural oedemas, dyspnoea during low activity, or basal crackles by lung stethoscopy
  • renal insufficiency with albumin excretion larger than 300 g/day
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00333671

Locations
Denmark
Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75
Herlev, Denmark, DK-2730
Sponsors and Collaborators
Glostrup University Hospital, Copenhagen
Investigators
Principal Investigator: Dorte Nellemann Thornit, MD Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Nordre Ringvej 57, DK-2600 Glostrup, Denmark
  More Information

No publications provided by Glostrup University Hospital, Copenhagen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Birgit Sander, Principal Investigator, Glostrup University Hospital, Copenhagen
ClinicalTrials.gov Identifier: NCT00333671     History of Changes
Other Study ID Numbers: Dorte Nellemann, glycerol
Study First Received: June 2, 2006
Last Updated: September 18, 2012
Health Authority: Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by Glostrup University Hospital, Copenhagen:
Macular oedema
Diabetes
Pathogenesis
Osmolality
Retinal thickness

Additional relevant MeSH terms:
Edema
Macular Edema
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on November 25, 2014