Ignite Creation Date:
2024-05-05 @ 5:10 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00409747
Status:
COMPLETED
Last Update Posted:
2015-12-11
First Post:
2006-12-08
Brief Title:
Minocycline to Treat Childhood Regressive Autism
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Treatment of Childhood Regressive Autism With Minocycline an Anti-Inflammatory Agent Active Within the CNS
Status:
COMPLETED
Status Verified Date:
2015-11
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:
There is a subgroup of children with autism that appears to develop typically for a period of time and then loses social or language skills or regresses A recent study by Vargas and co-workers at Johns Hopkins has demonstrated that this regressive type of autism is associated with chronic brain inflammation as shown by an abnormal production of inflammatory cytokines among other abnormalities
This present study will test the effectiveness of minocycline an antibiotic with anti-inflammatory properties in treating regressive autism Although behavioral therapies have improved some symptoms of autism there are no medical treatments for the disorder and many children have ongoing behavioral difficulties A medicine with anti-inflammatory properties may be beneficial for children with regressive autism
This will be an open-label trial meaning all children in this study will receive minocycline They will also receive vitamin B6 to reduce the possible chance of side effects of the minocycline
Children ages 3 to 12 with regressive autism may be eligible for this study The children will take minocycline and vitamin B6 daily for 6 months Prior to starting the medication and vitamin B6 children will receive a comprehensive diagnostic assessment for autism as well as a physical examination medical history and laboratory tests Children will then receive ongoing assessments to monitor their behavior communication language skills and medical issues at 2 weeks and at 1 2 4 6 and 12 months Children who respond to the treatment will receive an additional 3 months of minocycline and vitamin B6
This present study will test the effectiveness of minocycline an antibiotic with anti-inflammatory properties in treating regressive autism Although behavioral therapies have improved some symptoms of autism there are no medical treatments for the disorder and many children have ongoing behavioral difficulties A medicine with anti-inflammatory properties may be beneficial for children with regressive autism
This will be an open-label trial meaning all children in this study will receive minocycline They will also receive vitamin B6 to reduce the possible chance of side effects of the minocycline
Children ages 3 to 12 with regressive autism may be eligible for this study The children will take minocycline and vitamin B6 daily for 6 months Prior to starting the medication and vitamin B6 children will receive a comprehensive diagnostic assessment for autism as well as a physical examination medical history and laboratory tests Children will then receive ongoing assessments to monitor their behavior communication language skills and medical issues at 2 weeks and at 1 2 4 6 and 12 months Children who respond to the treatment will receive an additional 3 months of minocycline and vitamin B6
Detailed Description:
Autism is a neurodevelopmental disorder that results in abnormalities of social and language development and is associated with rigid and repetitive behaviors Although there is strong evidence of heritability the involved genes have not been identified The prevalence of autism spectrum disorders may be as common as 1 in 166 The average concordance rate in monozygotic twins is 70 suggesting that environmental factors play a role in the disease Subgroups of autistic children seem unusually sensitive to infections immunizations and dietary factors but none of these factors has been causally identified with the disease Nevertheless autoimmunity has been considered to play a role on the basis of indirect evidence There is no evidence-based efficacious treatment for autism
There is a subgroup of children with autism that appear to develop typically for a period of time and then lose skills or regress A recent study by Vargas and co-workers at Johns Hopkins has demonstrated that the regressive subtype of autism is associated with chronic brain neuroinflammation as exemplified by activation of microglia and astroglia and the abnormal production of inflammatory cytokines and growth factors assayed in both tissue samples brain banks and CS The authors remarked that these responses were similar to those seen in some neurodegenerative disorders such as amyotrophic lateral sclerosis and that chronic microglia activation appears to be responsible for a sustained neuroinflammatory response that facilitates the production of multiple neurotoxic mediators Chronic neuroglial activation could be the result of an abnormal persistence of a fetal development pattern In this scenario neuroglial activation could play a role in initiating and in maintaining the pathology Alternatively neuroglial activation may only be a secondary response to the initiating causal factors and not a direct effector of injury Since neuroglial activation requires the nuclear translocation of the pro-inflammatory transcription factor NF-kappa B and since inhibitors of NF-kappa-B with good CNS penetrance are available the role of neuroinflammation in initiating and sustaining the autistic condition can be probed
The antibiotic minocycline is a powerful inhibitor of microglial activation apparently through blockade of NF-kappa-B nuclear translocation Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis ALS and Huntingtons disease and has been recently shown to stabilize the course of Huntingtons disease in humans over a 2-year period
To evaluate the possibility of benefit in autistic children we propose to conduct an open-label trial of the anti-inflammatory antibiotic minocycline an agent that reduces inflammation by blocking the nuclear translocation of the proinflammatory transcription factor NF-kappa-B Minocycline is Food and Drug Administration FDA-approved for treatment of a variety of infections and has been widely used for the treatment of adolescent acne Minocycline is currently in phase III trials for the treatment of Huntingtons disease and amyotrophic lateral sclerosis
This proposal is for an initial 6-month single-arm off label open-label study with a 3 month extension phase offered to responders that will evaluate dose safety and efficacy of minocycline in 10 children ages 3 to 12 years with a primary diagnosis of autism and a history of developmental regression The subjects will be evaluated by a diagnosticbehavioral assessment and the extent of neuroinflammation judged by CSF cytokinechemokine profiles before and after the 6-month treatment Subjects will also be given 06 mgkg vitamin B6 twice a day as a prophylactic for possible minocycline induced nausea and vomiting If the results of this feasibility study are encouraging we expect to conduct a double-blind placebo-controlled trial of minocycline therapy
There is a subgroup of children with autism that appear to develop typically for a period of time and then lose skills or regress A recent study by Vargas and co-workers at Johns Hopkins has demonstrated that the regressive subtype of autism is associated with chronic brain neuroinflammation as exemplified by activation of microglia and astroglia and the abnormal production of inflammatory cytokines and growth factors assayed in both tissue samples brain banks and CS The authors remarked that these responses were similar to those seen in some neurodegenerative disorders such as amyotrophic lateral sclerosis and that chronic microglia activation appears to be responsible for a sustained neuroinflammatory response that facilitates the production of multiple neurotoxic mediators Chronic neuroglial activation could be the result of an abnormal persistence of a fetal development pattern In this scenario neuroglial activation could play a role in initiating and in maintaining the pathology Alternatively neuroglial activation may only be a secondary response to the initiating causal factors and not a direct effector of injury Since neuroglial activation requires the nuclear translocation of the pro-inflammatory transcription factor NF-kappa B and since inhibitors of NF-kappa-B with good CNS penetrance are available the role of neuroinflammation in initiating and sustaining the autistic condition can be probed
The antibiotic minocycline is a powerful inhibitor of microglial activation apparently through blockade of NF-kappa-B nuclear translocation Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis ALS and Huntingtons disease and has been recently shown to stabilize the course of Huntingtons disease in humans over a 2-year period
To evaluate the possibility of benefit in autistic children we propose to conduct an open-label trial of the anti-inflammatory antibiotic minocycline an agent that reduces inflammation by blocking the nuclear translocation of the proinflammatory transcription factor NF-kappa-B Minocycline is Food and Drug Administration FDA-approved for treatment of a variety of infections and has been widely used for the treatment of adolescent acne Minocycline is currently in phase III trials for the treatment of Huntingtons disease and amyotrophic lateral sclerosis
This proposal is for an initial 6-month single-arm off label open-label study with a 3 month extension phase offered to responders that will evaluate dose safety and efficacy of minocycline in 10 children ages 3 to 12 years with a primary diagnosis of autism and a history of developmental regression The subjects will be evaluated by a diagnosticbehavioral assessment and the extent of neuroinflammation judged by CSF cytokinechemokine profiles before and after the 6-month treatment Subjects will also be given 06 mgkg vitamin B6 twice a day as a prophylactic for possible minocycline induced nausea and vomiting If the results of this feasibility study are encouraging we expect to conduct a double-blind placebo-controlled trial of minocycline therapy
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-M-0024 | OTHER | NIH Protocol number | None |