Clinical trial NCT02144103: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
Sponsor class: OTHER_GOV
First posted: 2014-05-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: SAEs and SARs monitoring
timeFrame: 4 weeks after treatment
Secondary outcomes:
measure: Change in visual acuty
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Changes in structures of fundus of the eye-1
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Changes in structures of fundus of the eye-2
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Change in visual field
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Change in retinal flicker responce
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Change in intraocular pressure
timeFrame: Follow up to completion (up to 48 weeks after treatment)
measure: Quality of life monitoring
timeFrame: Follow up to completion (up to 48 weeks after treatment)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Institution "Outpatient Health Center №1" of the Business Administration for the President of the Russian Federation
city: Moscow
country: Russian Federation
facility: 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
Study officials:
affiliation: Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation
name: Alina K Drakon, MD
role: STUDY_DIRECTOR
affiliation: 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
name: Ilya I Eremin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Budgetary Institution "Outpatient Health Center №1" of the Business Administration for the President of the Russian Federation
name: Julia P Sotnikova, MD
role: PRINCIPAL_INVESTIGATOR
References: