Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000117
Status:
COMPLETED
Last Update Posted:
2009-09-17
First Post:
1999-09-23
Brief Title:
Intravenous Immunoglobulin Therapy in Optic Neuritis
Sponsor:
National Eye Institute NEI
Organization:
National Eye Institute NEI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2009-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To determine whether high-dose intravenous immunoglobulin IVIg is more effective than placebo in restoring lost visual function visual acuity in optic neuritis ON
To determine the time course of recovery following IVIg administration If the reports of IVIg-associated clinical improvement occurring within 3 to 6 months following treatment can be confirmed this would provide indirect evidence that IVIg may promote central nervous system CNS remyelination in optic neuritis and multiple sclerosis MS
To determine the time course of recovery following IVIg administration If the reports of IVIg-associated clinical improvement occurring within 3 to 6 months following treatment can be confirmed this would provide indirect evidence that IVIg may promote central nervous system CNS remyelination in optic neuritis and multiple sclerosis MS
Detailed Description:
Optic neuritis is the leading cause of transient spontaneous reversible visual loss in young adults Characteristically patients present with central visual loss that peaks within a few days and is often associated with eye pain Visual loss may be complete Spontaneous recovery usually begins within 4 weeks and marked recovery occurs within 1 to 3 months in most patients Although clinical improvement is the rule not all patients recover fully and many are left with residual symptoms Although there are limited pathological studies in inflammatory ON the pathological changes are thought to be virtually identical with those seen in MS with disruption of the blood-nerve brain barrier primary demyelination with axonal sparing variable degrees of lymphocytic infiltration an abundance of macrophages around the inflammatory demyelination lesion various degrees of remyelination and later oligodendrocyte loss axonal loss and gliosis
Remyelination by oligodendrocytes occurs early in the MS lesion as documented by myelin sheaths that are abnormally thin relative to axon diameter These thin myelin sheaths are often seen prominently at the edge of demyelinated plaques A recent series of studies has shown that within weeks of the initial event there is extensive oligodendrocyte regeneration and remyelination These immature oligodendrocytes express a series of developmentally restricted antigens This finding has been interpreted to suggest that the cells that repopulate the acute plaque and that affect remyelination are newly generated and not residual mature oligodendrocytes These observations support the possibility that factors that promote remyelination could be used to improve clinical recovery in ON and MS
Work at the Mayo Clinic has shown that both immunoglobulin G IgG directed against spinal cord antigens and purified polyclonal mouse IgG administered systemically promote extensive remyelination in SJL mice chronically infected with Theilers virus In addition tissue culture studies suggest that IgG directed against CNS components may promote oligodendroglial proliferation and differentiation Thus experimental evidence exists for the concept that immunoglobulins may stimulate the proliferation and differentiation of oligodendrocytes It is possible that myelin components on the surface of oligodendrocytes could function as receptors or components of receptors Antibodies could mimic endogenous ligands thereby inducing the proliferation or differentiation of these cells
In a preliminary open-label pilot study of patients with chronic steroid-unresponsive ON Drs van Engelen Hommes and colleagues suggested that improvement in visual recovery could be seen following IgG treatment in patients with chronic stable ON These encouraging but preliminary basic and clinical studies have prompted us to design a double-blind and placebo-controlled clinical trial of IVIg in patients with recently acquired but apparently permanent muscle paralysis from MS NS31506 and to develop this NEI-funded ON study U10EY1096301
In this randomized placebo-controlled double-blind clinical trial 60 patients were assigned to receive either IVIg or a placebo over a period of 3 months In order to be eligible patients who meet the inclusion criteria needed to have a stable loss of visual function unchanged between the pre-enrollment screening visit and the enrollment visit All patients wre re-examined at 3 6 9 and 12 months with the primary outcome being the impact of treatment on visual acuity at 6 months as determined by measurements on a retroilluminated Early Treatment Diabetic Retinopathy Study chart at 4 meters
One group of patients received 04 gkg Gammimmune N intravenously daily for 5 days and thereafter once a month for 3 months total eight infusions The other group of patients received infusions of 01 percent human serum albumin in 10 percent maltose placebo according to the identical protocol used for Gammimmune N
The primary outcome measure was improvement in Logmar visual acuity by an average of 02 at 6 months The secondary outcome measures included change in visual acuity at 3 9 and 12 months as determined on a retroilluminated ETDRS chart at 4 meters change in visual fields at 6 and 12 months change in visual evoked responses at 3 6 and 12 months and change in neurological examination EDSS FS AI at 3 6 9 and 12 months
Remyelination by oligodendrocytes occurs early in the MS lesion as documented by myelin sheaths that are abnormally thin relative to axon diameter These thin myelin sheaths are often seen prominently at the edge of demyelinated plaques A recent series of studies has shown that within weeks of the initial event there is extensive oligodendrocyte regeneration and remyelination These immature oligodendrocytes express a series of developmentally restricted antigens This finding has been interpreted to suggest that the cells that repopulate the acute plaque and that affect remyelination are newly generated and not residual mature oligodendrocytes These observations support the possibility that factors that promote remyelination could be used to improve clinical recovery in ON and MS
Work at the Mayo Clinic has shown that both immunoglobulin G IgG directed against spinal cord antigens and purified polyclonal mouse IgG administered systemically promote extensive remyelination in SJL mice chronically infected with Theilers virus In addition tissue culture studies suggest that IgG directed against CNS components may promote oligodendroglial proliferation and differentiation Thus experimental evidence exists for the concept that immunoglobulins may stimulate the proliferation and differentiation of oligodendrocytes It is possible that myelin components on the surface of oligodendrocytes could function as receptors or components of receptors Antibodies could mimic endogenous ligands thereby inducing the proliferation or differentiation of these cells
In a preliminary open-label pilot study of patients with chronic steroid-unresponsive ON Drs van Engelen Hommes and colleagues suggested that improvement in visual recovery could be seen following IgG treatment in patients with chronic stable ON These encouraging but preliminary basic and clinical studies have prompted us to design a double-blind and placebo-controlled clinical trial of IVIg in patients with recently acquired but apparently permanent muscle paralysis from MS NS31506 and to develop this NEI-funded ON study U10EY1096301
In this randomized placebo-controlled double-blind clinical trial 60 patients were assigned to receive either IVIg or a placebo over a period of 3 months In order to be eligible patients who meet the inclusion criteria needed to have a stable loss of visual function unchanged between the pre-enrollment screening visit and the enrollment visit All patients wre re-examined at 3 6 9 and 12 months with the primary outcome being the impact of treatment on visual acuity at 6 months as determined by measurements on a retroilluminated Early Treatment Diabetic Retinopathy Study chart at 4 meters
One group of patients received 04 gkg Gammimmune N intravenously daily for 5 days and thereafter once a month for 3 months total eight infusions The other group of patients received infusions of 01 percent human serum albumin in 10 percent maltose placebo according to the identical protocol used for Gammimmune N
The primary outcome measure was improvement in Logmar visual acuity by an average of 02 at 6 months The secondary outcome measures included change in visual acuity at 3 9 and 12 months as determined on a retroilluminated ETDRS chart at 4 meters change in visual fields at 6 and 12 months change in visual evoked responses at 3 6 and 12 months and change in neurological examination EDSS FS AI at 3 6 9 and 12 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None