Back to results

Effectiveness and Safety of Adipose-Derived Regenerative Cells for Treatment of Glaucomatous Neurodegeneration

Primary Purpose

Retinal Degeneration, Primary Open-Angle Glaucoma

Status

Unknown status

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

Subtenon administration of autologous ADRC

Liposuction

ADRC isolation

About this trial

This is an interventional treatment trial for Retinal Degeneration focused on measuring Glaucomatous Neurodegeneration, Retinal Degeneration, Primary Open-Angle Glaucoma, Optic Neuropathy, Intraocular pressure, Retinal ganglion cell degeneration, Optic nerve atrophy, Subtenon injection, Glaucomatous damage, ADRC, Adipose-derived regenerative cells, Fat tissue, Stem cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient suffers from primary open-angle glaucoma (II and III stages; singe eye or both eyes) at least for 6 months
Intraocular pressure is stable for at least for 3 months
Visual acuity of each eye (measured by using visual acuity charts projector) not less than 0,1
Patient is familiar with Participant information sheet
Patient signed informed consent form

Non-inclusion Criteria:

Contraindications to the local anesthesia or medical history of allergic reactions to local anesthetics
Any anomalies or conditions of at least one eye which can limit tonometry implementation
Inflammatory disease of at least one eye or auxiliary apparatus (both infectious and non-infectious etiology: conjunctivitis, keratitis, uveitis, dacryocystitis etc.)
Medical history of surgery on at least one eye during preceding 6 months.
Medical history of heavy traumatic injury of eyes
Patient has a cataract with high degree of lens opacification which can limit planned eye examination
Patient prescribed for systemic corticosteroids or other medications treatment with proven effect leading on intraocular pressure increase
Medical history or present dry eye syndrome accompanied by corneal and conjunctival xerosis
Subcompensated or decompensated forms of chronic diseases of internal organs
Clinically significant abnormalities in results of laboratory tests
Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.)
Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion
Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy.
Patient's activated partial thromboplastin time exceeds normal levels more than 1,8 times
Patients prescribed for anticoagulants treatment or patient received anticoagulants at least one hour prior lipoaspiration
Medical history of heterotopic ossifications
Patients prescribed for glycoprotein inhibitors treatment
Acute vascular pathology
Age-related macular degeneration

Exclusion Criteria:

Patient's refusal from the further participation in trial
Patient's refusal from compliance with the requirements of contraception during the participation in research
Chronic kidney disease IV- V stages (creatinine clearance < 30 mL/min estimated by Cockroft-Gault formula)
Confirmed syphilis, HIV, hepatitis B or C infections

Dropout Criteria:

Direct indications on immediate initiation of treatment with medications with proven effect leading to intraocular pressure increase
Pregnancy
Development of cataract with high degree of lens opacification which can limit planned eye examination

Sites / Locations

Federal State Budgetary Institution "Outpatient Health Center №1" of the Business Administration for the President of the Russian Federation
Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ADRC injection

Arm Description

Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate adipose-derived regenerative cells (ADRC). After ADRC isolation autologous cells suspension will be injected into subtenon space of patient's eye.

Outcomes

Primary Outcome Measures

SAEs and SARs monitoring

Types, probability and severity of treatment emergent serious adverse events (SAEs) and serious adverse reactions (SARs)

Secondary Outcome Measures

Change in visual acuty

Change from baseline in visual acuity assessed by visual acuty test

Changes in structures of fundus of the eye-1

Changes in structures of fundus of the eye assessed by funduscopy: changes of configuration and size of optic disc, neuroretinal rim thinning, degree of optic disc pallor, hemorrhages on the optic nerve and retina, vascular changes, presence of degenerative changes of retina, optic disc drusen, edema and retinal detachment.

Changes in structures of fundus of the eye-2

Changes in structures of fundus of the eye assessed by optical coherence tomography: changes of optic disc, neuroretinal rim and macula, retinal nerve fiber layer thickness.

Change in visual field

Change from baseline in visual field assessed by computer perimetry

Change in retinal flicker responce

Change from baseline in critical flicker fusion threshold

Change in intraocular pressure

Change from baseline in intraocular pressure assessed by pneumotonometry and tonography

Quality of life monitoring

Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36)., Visual Functioning-14 Quality of Life (VF-14 QOL) and Glaucoma Quality of Life-15 (GQL-15)

Full Information

NCT ID

NCT02144103

First Posted

May 9, 2014

Last Updated

July 19, 2017

Sponsor

Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

1. Study Identification

Unique Protocol Identification Number

NCT02144103

Brief Title

Effectiveness and Safety of Adipose-Derived Regenerative Cells for Treatment of Glaucomatous Neurodegeneration

Official Title

Effectiveness and Safety of Subtenon Administration of Autologous Adipose-Derived Regenerative Cells for Treatment of Glaucomatous Neurodegeneration

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Unknown status

Study Start Date

May 2014 (Actual)

Primary Completion Date

July 2018 (Anticipated)

Study Completion Date

January 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front abdominal wall. ADRC will be administered one-time into subtenon space of patient's eyeball. This is a single arm study with no control. All patients receive cell therapy.

Detailed Description

Fat tissue obtainment: Subjects will undergo liposuction under local anesthesia. In this procedure, Ringer's solution with the anesthetic lidocaine and vasoconstrictor adrenaline infused into the adipose compartment to minimize blood loss and contamination of the tissue by peripheral blood cells. 15 minutes later a hollow blunt-tipped 3 mm cannula introduced into the subcutaneous space through small (0.5 cm) incision. The cannula attached to syringe and under gentle suction moved through the adipose compartment, mechanically disrupting the fat tissue. Aspirate volume - approximately 150-200 cc. Procedure time - 30 minutes. ADRC isolation: Aspirated fat tissue placed into sterile vessel which inserted into Celution 800/CRS System (Cytori Therapeutics Inc) - closed system for automated and standardized extraction and concentration of ADRC. Celution 800/CRS System drains excess of fluid from fat tissue and estimate it's volume After that lipoaspirate washed extensively with equal volumes of Ringer's solution to remove blood. At the end of this process System indicates required volume of enzyme reagent (Celase®) which should be added immediately by operator. After enzyme treatment Celution 800/CRS System automatically transfers isolated ADRC into washing compartment where ADRC washed and concentrated in 5 mL suspension. Tissue processing time - approximately 60 minutes. ADRC suspension match all requirements listed in technical documentation for Celution 800/CRS System. Obtained ADRC divided into 2 portions. First portion (0.2-0.5 mL) used for counting, viability and sterility assessment. Second portion placed into sterile syringe for injection. Subtenon injection of ADRC: Antiseptic and anesthetic solutions instilled into conjunctival sac. After that blepharostat installed. The patient is asked to look in opposite to the injection side direction. Doctor inserts a needle into inferior temporal quadrant between rectus muscles,10-12 mm from the limbus. Needle should be moved slowly, as close as possible to the eyeball. After needle placement at the depth of 5-7 mm doctor injects concentrated solution of ADRC (up to 0,5 ml per single injection). Injection is made by insulin syringe with a needle size 0.45 mm * 12mm (26 G).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Retinal Degeneration, Primary Open-Angle Glaucoma

Keywords

Glaucomatous Neurodegeneration, Retinal Degeneration, Primary Open-Angle Glaucoma, Optic Neuropathy, Intraocular pressure, Retinal ganglion cell degeneration, Optic nerve atrophy, Subtenon injection, Glaucomatous damage, ADRC, Adipose-derived regenerative cells, Fat tissue, Stem cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ADRC injection

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Subtenon administration of autologous ADRC

Intervention Type

Procedure

Intervention Name(s)

Liposuction

Intervention Type

Device

Intervention Name(s)

ADRC isolation

Intervention Description

ADRC isolation performed using Celution 800/CRS System (Cytori Therapeutics Inc) according to manufacturer's protocol

Primary Outcome Measure Information:

Title

SAEs and SARs monitoring

Description

Types, probability and severity of treatment emergent serious adverse events (SAEs) and serious adverse reactions (SARs)

Time Frame

4 weeks after treatment

Secondary Outcome Measure Information:

Title

Change in visual acuty

Description

Change from baseline in visual acuity assessed by visual acuty test

Time Frame