Ignite Creation Date:
2025-12-24 @ 11:52 PM
Ignite Modification Date:
2025-12-25 @ 9:47 PM
Study NCT ID:
NCT01469351
Status:
COMPLETED
Last Update Posted:
2013-04-19
First Post:
2011-11-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Identifying Potential Effects of Liraglutide on Degenerative Changes
Sponsor:
University of Aarhus
Organization:
Study Overview
Official Title:
Neurodegenerative Changes in Alzheimer's Disease: Identifying Potential Effects of Liraglutide on Degenerative Changes
Status:
COMPLETED
Status Verified Date:
2013-04
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:
Today Alzheimers disease can not be cured. Animal experiments have shown that the hormone GLP-1 can improve memory in Alzheimer-prone mice.
The investigators hypothesis is that a 6-month treatment with the GLP-1 receptor stimulating drug liraglutide will reduce the intracerebral amyloid deposition in the central nervous system (CNS) in patients with Alzheimer's disease (AD) and thereby reduce the clinical symptoms of the disease.
The investigators hypothesis is that a 6-month treatment with the GLP-1 receptor stimulating drug liraglutide will reduce the intracerebral amyloid deposition in the central nervous system (CNS) in patients with Alzheimer's disease (AD) and thereby reduce the clinical symptoms of the disease.
Detailed Description:
The incidences of both type 2 diabetes (DM-2) and Alzheimer's disease (AD) have increased during the last years, resulting in an increase in morbidity and mortality. DM-2 is a risk factor for both AD and vascular dementia. In addition, an increased incidence of DM-2 in Alzheimer's patients has been observed. The understanding of the underlying mechanism behind this linkage is so far very sparse.
In both diseases premature cell degeneration develops. DM-2 is characterized by a loss of β-cell function and β cell mass in the pancreas, whereas AD shows a loss of neuronal function as well as neuronal cell death. General metabolic risk factors such as hyperglycemia and hypercholesterolemia are evident in both diseases.
Glucagon-like-peptide-1 (GLP-1) is an incretin hormone with numerous documented effects on the glycaemic response. It is released as a response to food ingestion and consequently exerts a glucose-dependent stimulation of insulin secretion while inhibiting glucagon secretion. In animal experiments as well as cell experiments β-cell neogenesis, growth and differentiation are stimulated by GLP-1, and inhibition of β-cell apoptosis has been demonstrated in cell studies. In addition to α- and β-cells of the pancreas, GLP-1 receptors (GLP-1R) have been localized to the CNS, where GLP-1R are distributed corresponding to the hypothalamus and hippocampus. Experimental investigations on mice where GLP-1 was given intra-cerebroventricularly, GLP-1R stimulation reduced nerve cell damage caused by neurotoxic stimuli. Furthermore, GLP-1R stimulation in hippocampus induced learning ability and memory and it has been shown that GLP-1R stimulation leeds to neurite outgrowth and protects against nerve cell apoptosis.
In connection with hyperinsulinaemia in early stages of DM-2, studies suggest that stimulation of insulin receptors represented in the brain produce an increased level of β-amyloid and an increased number of neurofibrillary tangles. AD is pathologically characterized by an increased level of β-amyloid as well as an increased number of neurofibrillar tangles. Accumulation of β-amyloid in the brain is localized to areas with cognitive functions. A recent animal experimental work has shown reduced memory in GLP-1 receptor KO mice and mentions the lack of a possible neuroprotective effect as a potential explanation for the observation. In studies of humans a worsening of the cognitive functions has been shown to be associated with dementia and DM-2, even though an actual causal relation has not yet been found. The investigators have recently shown that GLP-1 has a neuroprotective function in patients with DM-2.
Positron emission tomography (PET) scanning has been well evaluated in clinical demonstration of CNS changes following AD including changes in amyloid deposits.
Presently there are no registered drugs which change the deposition of amyloid and there are no drugs with convincing effect on the progression of the disease in patients with Alzheimer's. Moreover the drugs which have been marketed for treatment have a disadvantageous side effect profile. Besides insulin, β-cells secrete amylin, amyloid or IAPP (islet amyloid polypeptide) and these thus share certain characteristics with β-amyloid. Previously IAPP was considered to be non-toxic but recent studies have indicated a possible conversion to toxic β-amyloid.
The insulin-producing β-cells have been found to be characterized by accumulation of amyloid in several DM-2 models. A recent study with treatment with DPP-4 inhibitors (increasing endogenous GLP-1) improved glucose tolerance, increased GLP-1 levels and normalized the topography of the islets of Langerhans in a mouse model with β cell specific over expression of human amyloid.
The investigators hypothesis is that a 26 week treatment with the GLP-1 receptor stimulating pharmaceutical liraglutide will reduce the intracerebral amyloid deposition in the CNS in patients with Alzheimer's disease, as demonstrated by PET.
The investigators aim is that this clinical study will be able to give new information about the effect of the GLP-1 axis in the CNS and explore the potential for treatment of large groups of patients who cannot be offered effective drugs today. Altogether the results from the studies will contribute to the development of future treatment options for AD.
In both diseases premature cell degeneration develops. DM-2 is characterized by a loss of β-cell function and β cell mass in the pancreas, whereas AD shows a loss of neuronal function as well as neuronal cell death. General metabolic risk factors such as hyperglycemia and hypercholesterolemia are evident in both diseases.
Glucagon-like-peptide-1 (GLP-1) is an incretin hormone with numerous documented effects on the glycaemic response. It is released as a response to food ingestion and consequently exerts a glucose-dependent stimulation of insulin secretion while inhibiting glucagon secretion. In animal experiments as well as cell experiments β-cell neogenesis, growth and differentiation are stimulated by GLP-1, and inhibition of β-cell apoptosis has been demonstrated in cell studies. In addition to α- and β-cells of the pancreas, GLP-1 receptors (GLP-1R) have been localized to the CNS, where GLP-1R are distributed corresponding to the hypothalamus and hippocampus. Experimental investigations on mice where GLP-1 was given intra-cerebroventricularly, GLP-1R stimulation reduced nerve cell damage caused by neurotoxic stimuli. Furthermore, GLP-1R stimulation in hippocampus induced learning ability and memory and it has been shown that GLP-1R stimulation leeds to neurite outgrowth and protects against nerve cell apoptosis.
In connection with hyperinsulinaemia in early stages of DM-2, studies suggest that stimulation of insulin receptors represented in the brain produce an increased level of β-amyloid and an increased number of neurofibrillary tangles. AD is pathologically characterized by an increased level of β-amyloid as well as an increased number of neurofibrillar tangles. Accumulation of β-amyloid in the brain is localized to areas with cognitive functions. A recent animal experimental work has shown reduced memory in GLP-1 receptor KO mice and mentions the lack of a possible neuroprotective effect as a potential explanation for the observation. In studies of humans a worsening of the cognitive functions has been shown to be associated with dementia and DM-2, even though an actual causal relation has not yet been found. The investigators have recently shown that GLP-1 has a neuroprotective function in patients with DM-2.
Positron emission tomography (PET) scanning has been well evaluated in clinical demonstration of CNS changes following AD including changes in amyloid deposits.
Presently there are no registered drugs which change the deposition of amyloid and there are no drugs with convincing effect on the progression of the disease in patients with Alzheimer's. Moreover the drugs which have been marketed for treatment have a disadvantageous side effect profile. Besides insulin, β-cells secrete amylin, amyloid or IAPP (islet amyloid polypeptide) and these thus share certain characteristics with β-amyloid. Previously IAPP was considered to be non-toxic but recent studies have indicated a possible conversion to toxic β-amyloid.
The insulin-producing β-cells have been found to be characterized by accumulation of amyloid in several DM-2 models. A recent study with treatment with DPP-4 inhibitors (increasing endogenous GLP-1) improved glucose tolerance, increased GLP-1 levels and normalized the topography of the islets of Langerhans in a mouse model with β cell specific over expression of human amyloid.
The investigators hypothesis is that a 26 week treatment with the GLP-1 receptor stimulating pharmaceutical liraglutide will reduce the intracerebral amyloid deposition in the CNS in patients with Alzheimer's disease, as demonstrated by PET.
The investigators aim is that this clinical study will be able to give new information about the effect of the GLP-1 axis in the CNS and explore the potential for treatment of large groups of patients who cannot be offered effective drugs today. Altogether the results from the studies will contribute to the development of future treatment options for AD.
Study Oversight
Has Oversight DMC:
True
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?: