Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00031018
Status:
UNKNOWN
Last Update Posted:
2008-02-05
First Post:
2002-02-20
Brief Title:
Prevention of Cognitive Decline in Alzheimers Disease by Ingested Interferon Alpha
Sponsor:
National Center for Research Resources NCRR
Organization:
National Center for Research Resources NCRR
Study Overview
Official Title:
Prevention of Cognitive Decline in Alzheimers Disease by Ingested Interferon Alpha
Status:
UNKNOWN
Status Verified Date:
2008-02
Last Known Status:
ACTIVE_NOT_RECRUITING
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:
In this phase I-II parallel design randomized double-blind clinical trial we will determine if 3000 or 30000 units ingested hrIFN-a prevents deterioration of cognitive functioning in patients with dementia of Alzheimers type AD and whether ingested hrIFN-a treatment decreases acute phase reactants and pro-inflammatory cytokine IL-6 in mild to moderate AD We predict that the novel anti-inflammatory agent ingested human recombinant interferon alpha hrIFN-a will modulate inflammation and inhibit the natural history of AD progression If you are eligible you will receive Aricept for 5 weeks donezepil and thereafter in addition to Aricept either placebo inactive substance or interferon alpha at 3000 or 30000 units every day for 12 months
Detailed Description:
Inflammatory mechanisms contribute to neurodegeneration in AD Acute phase proteins such as the antichymotrypsin a1ACT pro-inflammatory cytokines IL-6 and IL-1 and activated microglial cells are all associated with neuritic plaques a1ACT levels are elevated in AD correlate with cognitive decline and serve as a biological marker of intervention a1ACT is intimately associated with the 42-AA b peptide Ab in filamentous amyloid deposits and stimulates the polymerization of Ab into amyloid filaments IL-6 is found in AD cortices prior to the onset of neuritic change serum and stimulated PMNC IL-6 levels are higher in AD and may induce b-amyloid protein deposition Microglia CNS resident inflammatory cells produce IL-6 within the adult human brain are IL-1a and are a prominent component of the neuritic plaque Because the pathogenesis of AD appears in part immune mediated we propose testing directly in humans whether ingested IFN-a can ameliorate AD Because there is no good model for inflammation in animal models of AD we will directly determine in humans 1 if 3000 or 30000 IU hrIFN-a inhibits the natural history rate of cognitive decline in mild to moderate AD using neuropsychological instruments as primary and secondary outcome measures that 2 correlates with inhibition of acute phase reactants and pro-inflammatory IL-6 If this novel anti-inflammatory agent inhibits the natural history rate of cognitive decline in AD in this pilot phase II trial this would provide the preliminary data to submit a phase III clinical trial
IFNs administered by the oral route show a systemic effect Oral IFN-a caused neutropenia in mice In contrast to their ip administration oral IFN-a did not result in the presence of detectable levels of IFNs in the blood Circulating specific antibody to IFN blocked the neutropenic effects of ip IFN but did not block the neutropenic effects of the oral IFNs 2 Therefore we examined the expression of antiviral MxA message a type 1 IFN-specific induced signal as a sensitive marker for type 1 IFN interaction with lymphoid cells in the gut-associated lymphoid tissue GALT using semi-quantitative RT-PCR on splenocytes from mice and PMNC from man after IFN-a ingestion Both mice and man demonstrated inducible levels of Mx mRNA after ingesting IFN-a Murine spleen T cells and CD8 T cells also demonstrated upregulation of Mx mRNA Therefore ingested IFN-a acts via established pathways of type 1 IFN signalling 3 Elevated levels of activated T cells mainly of the CD8 cytotoxicsuppressor phenotype are found in AD brains in contact with microglial cells 4 Interestingly peripheral CD8 T cells are depleted in AD patients 5 Lymphocytes bearing T helper and T cytotoxicsuppressor cell antigens are found in hippocampus and temporal cortex in AD 67 The data above suggest that lymphocytes are part of inflammation in AD and potential immunomodulatory T and CD8 T cells that contact ingested non-absorbed IFN in the GALT could migrate to the brain and decrease inflammation
IFNs administered by the oral route show a systemic effect Oral IFN-a caused neutropenia in mice In contrast to their ip administration oral IFN-a did not result in the presence of detectable levels of IFNs in the blood Circulating specific antibody to IFN blocked the neutropenic effects of ip IFN but did not block the neutropenic effects of the oral IFNs 2 Therefore we examined the expression of antiviral MxA message a type 1 IFN-specific induced signal as a sensitive marker for type 1 IFN interaction with lymphoid cells in the gut-associated lymphoid tissue GALT using semi-quantitative RT-PCR on splenocytes from mice and PMNC from man after IFN-a ingestion Both mice and man demonstrated inducible levels of Mx mRNA after ingesting IFN-a Murine spleen T cells and CD8 T cells also demonstrated upregulation of Mx mRNA Therefore ingested IFN-a acts via established pathways of type 1 IFN signalling 3 Elevated levels of activated T cells mainly of the CD8 cytotoxicsuppressor phenotype are found in AD brains in contact with microglial cells 4 Interestingly peripheral CD8 T cells are depleted in AD patients 5 Lymphocytes bearing T helper and T cytotoxicsuppressor cell antigens are found in hippocampus and temporal cortex in AD 67 The data above suggest that lymphocytes are part of inflammation in AD and potential immunomodulatory T and CD8 T cells that contact ingested non-absorbed IFN in the GALT could migrate to the brain and decrease inflammation
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