Von Hippel-Lindau SyndromePhase 1NCT00089765
Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome
A Phase 1 study testing Ranibizumab in people with Von Hippel-Lindau Syndrome, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
This study will examine whether he drug ranibizumab can slow or stop the growth of angiomas (blood vessel tumors) in patients with Von Hippel-Lindau syndrome (VHL). Angiomas commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Von Hippel-Lindau Syndrome
- What is being tested?
- Ranibizumab
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2004to 15 Aug 2007
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must understand and sign the informed consent.
- Participant must be at least 18 years of age.
- Participant must have retinal angiomas secondary to VHL in one or both eyes.
- Participant must have either optic nerve tumors or peripheral tumors that have caused central vision loss of 20/40 or worse.
- Participant must have clear ocular media and adequate papillary dilation to permit good quality stereoscopic fundus photography.
- All women of childbearing potential must have a negative urine pregnancy test at baseline, and be willing to undergo urine pregnancy testing immediately prior to each injection, and monthly for at least 2 months following the last dose of ranibizumab.
- Women of child-bearing potential who are sexually active and men who are sexually active are required to use two forms of birth control during the course of the study.
Who cannot join
- History (within past 5 years) or evidence of severe cardiac disease (apparent in electrocardiogram abnormalities, clinical history of unstable angina, acute coronary syndrome, myocardial infarction, revascularization procedure within 6 months prior to baseline, atrial or ventricular tachyarrythmias requiring ongoing treatment).
- History of stroke within 12 months of study entry.
- History within the past five years of a chronic ocular or periocular infection (including any history of ocular herpes zoster).
- Current acute ocular or periocular infection.
- Any major surgical procedure within one month of study entry.
- Known serious allergies to fluorescein dye.
Show all 11Show fewer
- Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, Protein Kinase C inhibitors, etc).
- Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye.
- History of vitrectomy surgery in the study eye.
- History of glaucoma filtering surgery in the study eye.
- History of corneal transplant in the study eye.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Intravitreal Injection of Ranibizumab (rhuFAB V2) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease
This study will examine whether he drug ranibizumab can slow or stop the growth of angiomas (blood vessel tumors) in patients with Von Hippel-Lindau syndrome (VHL). Angiomas commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Although these tumors are not cancerous, they may cause significant vision loss. Current treatments, including laser therapy, cryotherapy, and vitrectomy, may not be successful or possible for all patients. Ranibizumab decreases production of VEGF, a growth factor that is important for the formation of new blood vessels and that is elevated in patients with VHL. Preliminary findings from other studies suggest that ranibizumab can reduce retinal thickening caused by vessel and tumor growth and improve vision.
Patients 18 years of age and older with retinal angiomas due to VHL in one or both eyes and central vision loss of 20/40 or worse may be eligible for this study. Participants undergo the following tests and procedures:
Read more
- Medical history, physical examination, electrocardiogram (EKG) and blood tests.
- Eye examination, including eye pressure measurement and dilation of the pupils to examine the retina.
- Fluorescein angiography to evaluate the eye's blood vessels. For this test, a yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
- Optical coherence tomography to measure retinal thickness. The eyes are examined through a machine that produces cross-sectional pictures of the retina. These measures are repeated during the study to determine changes, if any, in retinal thickening.
- Stereoscopic color fundus photography to examine the back of the eye. The pupils are dilated with eye drops to examine and photograph the back of the eye.
- Electroretinogram (ERG) to measure electrical responses generated from within the retina. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside an open white globe that emits a series of light flashes for about 20 minutes. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Ranibizumab injections to treat ocular angiomas. Ranibizumab is injected through a needle into the eye's vitreous (gel-like substance that fills the inside of the eye). Seven injections are given over a 28-week period. Before each injection, the surface of the eye is numbed with anesthetic eye drops. This is followed by injection of another anesthetic into the lower portion of the eye in the clear tissue surrounding the white of the eye. After a few minutes, the ranibizumab is injected into the vitreous. Patients receive ranibizumab injections at the first visit (during enrollment) and again at 4, 8, 12, 16, 20 and 24 weeks after the first injection. At the 28-week visit, the doctor will determine if further treatment is needed. Patients can continue to have injections every 4 weeks until 1 year of follow-up (54 weeks).
At each injection visit, participants repeat most of the tests described above to evaluate the response to treatment and return a week later for another eye examination.
Read the detailed description
Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of an anti-VEGF therapy, ranibizumab (rhuFab V2) in 5 participants to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Participants will receive 7 intravitreal injections of study drug over a 6 month period, with the option of up to seven additional injections at the same dose and schedule during follow-up for a maximum period of 1 year after the initiation of treatment. The primary outcome will be a change in the best corrected visual acuity of 15 letters or more eight weeks after a participant receives the final study injection. The secondary outcomes will be a reduction in retinal thickening and leakage eight weeks after the participants receives the final study injection, and adverse events including local and systemic toxicities.
- Conditions
- Von Hippel-Lindau Syndrome
- Being tested
- Ranibizumab
- Keywords
- Retinal Angioma, Tumor, Anti-VEGF, Monoclonal Antibody, Macular Edema, Von Hippel-Lindau Disease, VEGF, Ranibizumab, VHL
- Medical subject headings
- von Hippel-Lindau Disease, Neoplasms, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RanibizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2004 (estimated)
- Study start10 Aug 2004
- Study completion15 Aug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Von Hippel-Lindau SyndromeStudies 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
- 5 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089765
- Sponsor's protocol ID
- 040240
- Other IDs
- 04-EI-0240
- Status last verified
- 15 Aug 2007
- First submitted
- 12 Aug 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Manski TJ, Heffner DK, Glenn GM, Patronas NJ, Pikus AT, Katz D, Lebovics R, Sledjeski K, Choyke PL, Zbar B, Linehan WM, Oldfield EH. Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. JAMA. 1997 May 14;277(18):1461-6. doi: 10.1001/jama.277.18.1461.
PubMed 9145719
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Intravitreal Injection of Ranibizumab (rhuFAB V2) for Advanced Ocular Disease of Von Hippel-Lindau (VHL) Disease
- ClinicalTrials.gov ID
- NCT00089765
- Acronym / sponsor ID
- 040240
- Conditions
- Von Hippel-Lindau Syndrome
- Keywords
- Retinal Angioma, Tumor, Anti-VEGF, Monoclonal Antibody, Macular Edema, Von Hippel-Lindau Disease, VEGF, Ranibizumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 10 Aug 2004
- Study completion
- 15 Aug 2007
- First posted
- 13 Aug 2004 (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 examine whether he drug ranibizumab can slow or stop the growth of angiomas (blood vessel tumors) in patients with Von Hippel-Lindau syndrome (VHL). Angiomas commonly develop in the back of the eye on the retina and the optic nerve in patients with VHL. Although these tumors are not cancerous, they may cause significant vision loss. Current treatments, including laser therapy, cryotherapy, and vitrectomy, may not be successful or possible for all patients. Ranibizumab decreases production of VEGF, a growth factor that is important for the formation of new blood vessels and that is elevated in patients with VHL. Preliminary findings from other studies suggest that ranibizumab can reduce retinal thickening caused by vessel and tumor growth and improve vision.
Patients 18 years of age and older with retinal angiomas due to VHL in one or both eyes and central vision loss of 20/40 or worse may be eligible for this study. Participants undergo the following tests and procedures:
- Medical history, physical examination, electrocardiogram (EKG) and blood tests.
- Eye examination, including eye pressure measurement and dilation of the pupils to examine the retina.
- Fluorescein angiography to evaluate the eye's blood vessels. For this test, a yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
- Optical coherence tomography to measure retinal thickness. The eyes are examined through a machine that produces cross-sectional pictures of the retina. These measures are repeated during the study to determine changes, if any, in retinal thickening.
- Stereoscopic color fundus photography to examine the back of the eye. The pupils are dilated with eye drops to examine and photograph the back of the eye.
- Electroretinogram (ERG) to measure electrical responses generated from within the retina. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside an open white globe that emits a series of light flashes for about 20 minutes. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Ranibizumab injections to treat ocular angiomas. Ranibizumab is injected through a needle into the eye's vitreous (gel-like substance that fills the inside of the eye). Seven injections are given over a 28-week period. Before each injection, the surface of the eye is numbed with anesthetic eye drops. This is followed by injection of another anesthetic into the lower portion of the eye in the clear tissue surrounding the white of the eye. After a few minutes, the ranibizumab is injected into the vitreous. Patients receive ranibizumab injections at the first visit (during enrollment) and again at 4, 8, 12, 16, 20 and 24 weeks after the first injection. At the 28-week visit, the doctor will determine if further treatment is needed. Patients can continue to have injections every 4 weeks until 1 year of follow-up (54 weeks).
At each injection visit, participants repeat most of the tests described above to evaluate the response to treatment and return a week later for another eye examination.
Detailed description
Von Hippel-Lindau Syndrome (VHL) is an autosomal dominant heritable disorder in which multiple benign and malignant neoplasms and cysts of specific histopathologies develop in the kidney, adrenal gland, pancreas, brain, spinal cord, eye, inner ear, epididymis, and broad ligament. Retinal angioma may be one of the earliest manifestations of VHL disease and may lead to a significant decrease in visual acuity of the affected individual. These tumors rarely regress spontaneously. The main cause of vision loss is retinal edema, specifically macular edema secondary to enlargement of peripheral retinal angiomas or angiomas found on or around the optic disk. Treatment of retinal angiomas depends on the location and size of the lesions but typically consists of photocoagulation or cryotherapy. However, there is no proven effective therapy for the treatment of VHL ocular lesions on or surrounding the optic nerve or lesions in the peripheral retina too large to respond to the traditional therapies. The genetic mutation found in VHL disease up-regulates the production of vascular endothelial growth factor (VEGF). Immunochemical studies of the VHL ocular lesions, as well as others found elsewhere in the body show marked increase in VEGF. This open-label study will pilot the use of an anti-VEGF therapy, ranibizumab (rhuFab V2) in 5 participants to investigate the potential efficacy as a treatment for retinal angiomas associated with VHL. Participants will receive 7 intravitreal injections of study drug over a 6 month period, with the option of up to seven additional injections at the same dose and schedule during follow-up for a maximum period of 1 year after the initiation of treatment. The primary outcome will be a change in the best corrected visual acuity of 15 letters or more eight weeks after a participant receives the final study injection. The secondary outcomes will be a reduction in retinal thickening and leakage eight weeks after the participants receives the final study injection, and adverse events including local and systemic toxicities.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
Key exclusion criteria (11 listed)
- History (within past 5 years) or evidence of severe cardiac disease (apparent in electrocardiogram abnormalities, clinical history of unstable angina, acute coronary syndrome, myocardial infarction, revascularization procedure within 6 months prior to baseline, atrial or ventricular tachyarrythmias requiring ongoing treatment).
- History of stroke within 12 months of study entry.
- History within the past five years of a chronic ocular or periocular infection (including any history of ocular herpes zoster).
- Current acute ocular or periocular infection.
- Any major surgical procedure within one month of study entry.
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 |
|---|---|---|
| Ranibizumab | 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 2 Jul 2017.
- Background: PubMed 9145719Manski TJ, Heffner DK, Glenn GM, Patronas NJ, Pikus AT, Katz D, Lebovics R, Sledjeski K, Choyke PL, Zbar B, Linehan WM, Oldfield EH. Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease. JAMA. 1997 May 14;277(18):1461-6. doi: 10.1001/jama.277.18.1461.
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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 Ranibizumab in people with Von Hippel-Lindau Syndrome, 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 7 inclusion and 11 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 2 Jul 2017. 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 NCT00089765, which also lists 1 linked publication.
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 2 Jul 2017.