Retinitis PigmentosaPhase 1NCT00063765
Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
A Phase 1 study testing Ciliary Neurotrophic Factor Implant NT-501 in people with Retinitis Pigmentosa, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will evaluate the safety of a ciliary neurotrophic factor (CNTF) implant placed in the eye to allow the release of CNTF directly on the retina. The results of this study may lead to a larger investigation of CNTF implants to treat retinitis pigmentosa (RP), a progressive degenerative eye disease that begins… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- Ciliary Neurotrophic Factor Implant NT-501
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Mar 2006
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To participate in this study, the participant must understand and sign the protocol's informed consent (if the participant's vision is impaired to the point where it is not possible to read the informed consent document, the informed consent document will be read in its entirety to the participant).
- Paticipant diagnosis consistent with retinitis pigmentosa (RP) characterized by the following features:
- progressive photoreceptor dysfunction an death
- clinical degeneration of the outer retina
- intraretinal 'bone-spicule' pigment
- visual field constriction
Show all 12Show fewer
- night blindness
- major reduction of both rod and cone electroretinogram (ERG) responses.
- The first two participants have 20/400 vision or worse in the implant (study) eye with the same or better in the fellow eye, while the remainder of the participants will have visual acuity of 20/100 or worse.
- Participant has an ERG less than 2 MV(28-32 Hz flicker)
- Participant with central visual field of 40 degrees diameter or less with the Goldmann V 4e stimulus (independent of a peripheral crescent of any size)
- Participant medically able to undergo ophthalmic surgery.
Who cannot join
- Participant less than 18 years of age.
- Participant medically unable to comply with study procedures or follow-up visits.
- Participant has glaucoma.
- Participant is receiving oral or other insulin treatment for diabetes.
- Participant has cataract and it interferes with the assessment of the posterior segment inflammation using a standard slit lamp examination.
- Participant has undergone intra-ocular lens replacement less than 6 months prior to enrollment.
Show all 14Show fewer
- Participant has participated in any other clinical trial of a drug or device within the last 6 months.
- Participant is on chemotherapy.
- Participant is on ocular medications known to be toxic to the lens, retina, or optic nerve.
- Participant who is pregnant.
- Participant with retinal inflammatory diseases.
- Participant with macula edema
- Participant with history of malignancy (except study participants having a basal cell carcinoma that was treated successfully, or other malignancy operated on and in remission of 5 years prior to inclusion in the trial).
- Participant is considered immunodeficient or has a known history of HIV.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Eye Institute (NEI)
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of NT-501-10 and NT-501-6A.02, Implants of Encapsulated Human NTC-210 Cells Releasing Ciliary Neurotrophic Factor (CNTF), in Patients With Retinitis Pigmentosa
This study will evaluate the safety of a ciliary neurotrophic factor (CNTF) implant placed in the eye to allow the release of CNTF directly on the retina. The results of this study may lead to a larger investigation of CNTF implants to treat retinitis pigmentosa (RP), a progressive degenerative eye disease that begins with loss of peripheral vision and night blindness and often leads to blindness in later life.
Currently, there are no effective treatments for RP. Researchers have found, however, that certain proteins, called ciliary neurotrophic factor (CNTF), can partially protect cells in the eye if given directly inside the eye. A major challenge in treating RP is to deliver medicine directly into the eye. One way to ensure that CNTF gets into the eye is to surgically place an implant inside the eye to release the protein.
Read more
Patients 18 years of age and older with retinitis pigmentosa whose visual acuity is 20/100 or worse may be eligible for this study. Candidates will be screened with a medical history, physical examination, eye examinations, and eye photographs. The eye examination includes measurement of visual acuity and eye pressure, examination of the pupils and eye movements, and examination of the lens and back of the eye. In addition, patients will have the following tests:
- Visual field test: Patients look at a central spot on a white screen and tell the examiner whenever they see a small light appear at other places on the screen.
- Electroretinogram (ERG): Electrodes are taped to the patient's forehead. Special contact lenses are placed on the eyes, similar to normal contact lenses, after the eye has been numbed with drops. The contact lenses sense small electrical signals generated by the retina. The ERG measures the electrical activity of the retina when it is stimulated by light. For the ERG recording, the patient looks inside a large, hollow, dark sphere, and sees flashes of light, first in the dark, and then with a light turned on in the sphere.
- Optical coherence tomography: This test, done with the machine used to examine the eye, measures retinal thickness by producing cross-sectional pictures of the retina.
Participants undergo surgery at the NIH Clinical Center in a 30-minute operation to place the implant in one eye. The surgery is done under local anesthetic. Before the procedure, patients are given a steroid injection along side the eye to minimize inflammation after surgery. Following the procedure, patients return for follow-up visits once a month for 6 months. At these visits, several of the exams described above are repeated to evaluate treatment effects and check for adverse side effects. After 6 months, the implant is surgically removed. Post-surgical care for both implant and explant surgeries include examinations the day and week after surgery to examine the wound, a high dose of steroid immediately after surgery, oral antibiotics for 7 days, and eye drops for 1 week to prevent infection and inflammation.
Read the detailed description
Retinitis Pigmentosa (RP) is a group of incurable degenerative diseases of the retina that have a complex molecular etiology. Approximately 100,000 Americans suffer from inherited retinal degenerative RP. More than 100 RP-inducing mutations have been identified in several genes including: rhodopsin, the rod visual pigment; peripherin, a membrane structure protein; and PDEB, the beta subunit of rod cyclic GMP (cGMP) phosphodiesterase. However, the genotype is unknown for the majority of patients. Despite this genetic heterogeneity, there tends to be a common pattern of visual loss in patients with RP. Typically, patients experience disturbance in night vision early in life due to the degeneration of rod photoreceptors. The remaining cone photoreceptors become their mainstay of vision, but over the years and decades, the cones slowly degenerate, leading to blindness. These two phases of degeneration in the visual life of an RP patient may involve different underlying pathogenic mechanisms. Regardless of the initial causative defects, the end results are photoreceptor degeneration. This common pathogenesis pathway provides a target for therapeutic intervention.
To date, there are few available, effective treatments for retinal degenerative disorders. One major challenge is to deliver potential therapeutic agents to the back of the eye, in particular to the retina. The blood-eye barrier prevents the penetration of a variety of molecules to the neurosensory retina in a similar manner to the action of the blood-brain barrier, which exists between the central nervous system and systemic circulation. To overcome this challenge, Neurotech USA, Inc. (Neurotech) developed encapsulated cell technology (ECT), specifically the NT-501-10 and NT-501-6A.02 devices, to enable controlled, sustained delivery of therapeutic agents directly into the intra-ocular fluids and thus providing direct access to the retina. ECT utilizes cells encapsulated within a semi-permeable polymer device that secretes therapeutic factors directly into the vitreous. In addition, ECT devices can be retrieved, providing an added level of safety.
Histopathologic studies have demonstrated the possibility of growth factors, neurotrophic factors, and cytokines as therapeutics for RP. Specifically, ciliary neurotrophic factor (CNTF) has proven to be the most effective in reducing retinal degeneration. Therefore, the use of implanted NT-501-10 and NT-501-6A.02 devices, which secrete CNTF into the retina, may be beneficial in patients with RP and other retinal degenerative diseases.
This pilot study will assess the ophthalmic and systemic safety, and to some extent efficacy, of the novel intra-ocular NT-501-10 and NT-501-6A.02 implants in patients with RP and poor visual acuity in one eye. The main purpose of the study is to assess the safety of the NT-501-10 and NT-501-6A.02 implants. Secondary outcomes will include the anterior chamber cell scale and vitreous haze grading to measure inflammation, which may be caused by the implant. Other secondary outcome measures related to potential product performance are visual acuity, visual fields, electroretinograms (ERG), and optical coherence tomography (OCT3) to determine retinal thickness.
- Conditions
- Retinitis Pigmentosa
- Being tested
- Ciliary Neurotrophic Factor Implant NT-501
- Keywords
- NT-501, CNTF, Retinitis Pigmentosa, RP
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ciliary Neurotrophic Factor Implant NT-501Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2003 (estimated)
- Study startJun 2003
- Study completionMar 2006
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 Retinitis PigmentosaStudies 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 1
- Primary purpose
- Treatment
- Enrolment
- 10 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00063765
- Sponsor's protocol ID
- 030234
- Other IDs
- 03-EI-0234
- Status last verified
- Mar 2006
- First submitted
- 3 Jul 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med. 1996 Jun;2(6):696-9. doi: 10.1038/nm0696-696.
PubMed 8640564Aebischer P, Kato AC. Treatment of amyotrophic lateral sclerosis using a gene therapy approach. Eur Neurol. 1995;35(2):65-8. doi: 10.1159/000117095.
PubMed 7796839A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group. Clin Neuropharmacol. 1995 Dec;18(6):515-32. doi: 10.1097/00002826-199512000-00004.
PubMed 8681312Kauper K, McGovern C, Sherman S, Heatherton P, Rapoza R, Stabila P, Dean B, Lee A, Borges S, Bouchard B, Tao W. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7484-91. doi: 10.1167/iovs.12-9970.
PubMed 23049090
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of NT-501-10 and NT-501-6A.02, Implants of Encapsulated Human NTC-210 Cells Releasing Ciliary Neurotrophic Factor (CNTF), in Patients With Retinitis Pigmentosa
- ClinicalTrials.gov ID
- NCT00063765
- Acronym / sponsor ID
- 030234
- Conditions
- Retinitis Pigmentosa
- Keywords
- NT-501, CNTF, Retinitis Pigmentosa, RP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- Jun 2003
- Study completion
- Mar 2006
- First posted
- 4 Jul 2003 (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.
This study will evaluate the safety of a ciliary neurotrophic factor (CNTF) implant placed in the eye to allow the release of CNTF directly on the retina. The results of this study may lead to a larger investigation of CNTF implants to treat retinitis pigmentosa (RP), a progressive degenerative eye disease that begins with loss of peripheral vision and night blindness and often leads to blindness in later life.
Currently, there are no effective treatments for RP. Researchers have found, however, that certain proteins, called ciliary neurotrophic factor (CNTF), can partially protect cells in the eye if given directly inside the eye. A major challenge in treating RP is to deliver medicine directly into the eye. One way to ensure that CNTF gets into the eye is to surgically place an implant inside the eye to release the protein.
Patients 18 years of age and older with retinitis pigmentosa whose visual acuity is 20/100 or worse may be eligible for this study. Candidates will be screened with a medical history, physical examination, eye examinations, and eye photographs. The eye examination includes measurement of visual acuity and eye pressure, examination of the pupils and eye movements, and examination of the lens and back of the eye. In addition, patients will have the following tests:
- Visual field test: Patients look at a central spot on a white screen and tell the examiner whenever they see a small light appear at other places on the screen.
- Electroretinogram (ERG): Electrodes are taped to the patient's forehead. Special contact lenses are placed on the eyes, similar to normal contact lenses, after the eye has been numbed with drops. The contact lenses sense small electrical signals generated by the retina. The ERG measures the electrical activity of the retina when it is stimulated by light. For the ERG recording, the patient looks inside a large, hollow, dark sphere, and sees flashes of light, first in the dark, and then with a light turned on in the sphere.
- Optical coherence tomography: This test, done with the machine used to examine the eye, measures retinal thickness by producing cross-sectional pictures of the retina.
Participants undergo surgery at the NIH Clinical Center in a 30-minute operation to place the implant in one eye. The surgery is done under local anesthetic. Before the procedure, patients are given a steroid injection along side the eye to minimize inflammation after surgery. Following the procedure, patients return for follow-up visits once a month for 6 months. At these visits, several of the exams described above are repeated to evaluate treatment effects and check for adverse side effects. After 6 months, the implant is surgically removed. Post-surgical care for both implant and explant surgeries include examinations the day and week after surgery to examine the wound, a high dose of steroid immediately after surgery, oral antibiotics for 7 days, and eye drops for 1 week to prevent infection and inflammation.
Detailed description
Retinitis Pigmentosa (RP) is a group of incurable degenerative diseases of the retina that have a complex molecular etiology. Approximately 100,000 Americans suffer from inherited retinal degenerative RP. More than 100 RP-inducing mutations have been identified in several genes including: rhodopsin, the rod visual pigment; peripherin, a membrane structure protein; and PDEB, the beta subunit of rod cyclic GMP (cGMP) phosphodiesterase. However, the genotype is unknown for the majority of patients. Despite this genetic heterogeneity, there tends to be a common pattern of visual loss in patients with RP. Typically, patients experience disturbance in night vision early in life due to the degeneration of rod photoreceptors. The remaining cone photoreceptors become their mainstay of vision, but over the years and decades, the cones slowly degenerate, leading to blindness. These two phases of degeneration in the visual life of an RP patient may involve different underlying pathogenic mechanisms. Regardless of the initial causative defects, the end results are photoreceptor degeneration. This common pathogenesis pathway provides a target for therapeutic intervention.
To date, there are few available, effective treatments for retinal degenerative disorders. One major challenge is to deliver potential therapeutic agents to the back of the eye, in particular to the retina. The blood-eye barrier prevents the penetration of a variety of molecules to the neurosensory retina in a similar manner to the action of the blood-brain barrier, which exists between the central nervous system and systemic circulation. To overcome this challenge, Neurotech USA, Inc. (Neurotech) developed encapsulated cell technology (ECT), specifically the NT-501-10 and NT-501-6A.02 devices, to enable controlled, sustained delivery of therapeutic agents directly into the intra-ocular fluids and thus providing direct access to the retina. ECT utilizes cells encapsulated within a semi-permeable polymer device that secretes therapeutic factors directly into the vitreous. In addition, ECT devices can be retrieved, providing an added level of safety.
Histopathologic studies have demonstrated the possibility of growth factors, neurotrophic factors, and cytokines as therapeutics for RP. Specifically, ciliary neurotrophic factor (CNTF) has proven to be the most effective in reducing retinal degeneration. Therefore, the use of implanted NT-501-10 and NT-501-6A.02 devices, which secrete CNTF into the retina, may be beneficial in patients with RP and other retinal degenerative diseases.
This pilot study will assess the ophthalmic and systemic safety, and to some extent efficacy, of the novel intra-ocular NT-501-10 and NT-501-6A.02 implants in patients with RP and poor visual acuity in one eye. The main purpose of the study is to assess the safety of the NT-501-10 and NT-501-6A.02 implants. Secondary outcomes will include the anterior chamber cell scale and vitreous haze grading to measure inflammation, which may be caused by the implant. Other secondary outcome measures related to potential product performance are visual acuity, visual fields, electroretinograms (ERG), and optical coherence tomography (OCT3) to determine retinal thickness.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- To participate in this study, the participant must understand and sign the protocol's informed consent (if the participant's vision is impaired to the point where it is not possible to read the informed consent document, the informed consent document will be read in its entirety to the participant).
- Paticipant diagnosis consistent with retinitis pigmentosa (RP) characterized by the following features:
- The first two participants have 20/400 vision or worse in the implant (study) eye with the same or better in the fellow eye, while the remainder of the participants will have visual acuity of 20/100 or worse.
- Participant has an ERG less than 2 MV(28-32 Hz flicker)
- Participant with central visual field of 40 degrees diameter or less with the Goldmann V 4e stimulus (independent of a peripheral crescent of any size)
Key exclusion criteria (14 listed)
- Participant less than 18 years of age.
- Participant medically unable to comply with study procedures or follow-up visits.
- Participant has glaucoma.
- Participant is receiving oral or other insulin treatment for diabetes.
- Participant has cataract and it interferes with the assessment of the posterior segment inflammation using a standard slit lamp examination.
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 |
|---|---|---|
| Ciliary Neurotrophic Factor Implant NT-501 | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 8640564Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med. 1996 Jun;2(6):696-9. doi: 10.1038/nm0696-696.
- Background: PubMed 7796839Aebischer P, Kato AC. Treatment of amyotrophic lateral sclerosis using a gene therapy approach. Eur Neurol. 1995;35(2):65-8. doi: 10.1159/000117095.
- Background: PubMed 8681312A phase I study of recombinant human ciliary neurotrophic factor (rHCNTF) in patients with amyotrophic lateral sclerosis. The ALS CNTF Treatment Study (ACTS) Phase I-II Study Group. Clin Neuropharmacol. 1995 Dec;18(6):515-32. doi: 10.1097/00002826-199512000-00004.
- Derived from this study: PubMed 23049090Kauper K, McGovern C, Sherman S, Heatherton P, Rapoza R, Stabila P, Dean B, Lee A, Borges S, Bouchard B, Tao W. Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2012 Nov 1;53(12):7484-91. doi: 10.1167/iovs.12-9970.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ciliary Neurotrophic Factor Implant NT-501 in people with Retinitis Pigmentosa, run by National Eye Institute (NEI) at 1 site in United States.
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 12 inclusion and 14 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 4 Mar 2008. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00063765, 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 4 Mar 2008.