Minocycline to Treat Childhood Regressive Autism

NCT00409747 | Completed Phase 4 Results

• 2 other identifiers: 07002407-M-0024
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Autism; Minocycline; Regressive Autism

Keywords

Immunology; Microglia; NF-Kappa-B; Antibiotic; Autism; Minocycline; Regressive Autism

Outcome Measures

Primary Outcomes (1)

• z Score

  The Mann-Whitney U-test was used to compare pre-/post-treatment differences in analyte concentrations in serum, plasma and CSF. The Mann-Whitney U test generates a z-score test statistic with an associated p value. A negative z-statistic reflects a decrease in analyte level from pre- to post-treatment. Statistical significance level was set at 0.05. There is one test statistic (z-score) per analyte, reflecting the pre-post comparison across all subjects. Pre and post treatment measurements of csf analytes: TNF alpha, Il-6, CCL-2(MCP-1), CCL3 (MIP-1alpha), CCL5(RANTES), CXCL(IL-8), BDNF, CD40L, GDNF, HGF, Leptin

  Pre and post treatment with minocyline at 6 months for 10 subjects

Secondary Outcomes (1)

• Clinical Global Impressions Scale-Severity (CGI). (Connors & Barkley, 1985)

  Baseline and 6 months

Study Arms (1)

Minocycline

EXPERIMENTAL

Drug: Minocycline

Interventions

Minocycline DRUG

Minocycline

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The sample will be children with:
• Diagnosis of idiopathic autism and regression
• Age between 3 and 12 years
• Willingness to undergo lumbar puncture for evaluation of proinflammatory CSF cytokines
• Stable behavioral plus or minus medication therapies.

You may not qualify if:

• Significant prematurity at birth (less than 32 weeks gestation); or birthweight significantly below normal for gestational age (SGA--small for gestational age).
• Neurologic disorders including cerebral palsy, uncontrolled epilepsy, and Landau-Kleffner syndrome.
• Evidence of renal insufficiency or hepatic disease (to reduce the incidence of side-effects, since minocycline is excreted by the kidneys following hepatic metabolism)
• Increased risk of developing lupus-like syndrome with minocycline administration (positive anti-double stranded DNA or anti-nucleosome antibody tests at baseline, or presence of a first degree relative with S.L.E.)
• Recent (less than two months prior to study entry) initiation of a behavioral therapy program or new psychotropic medication trial.
• Subjects on one of the medications/supplements listed as those with possible interactions or those on high dose B6 supplementation. For those families who are interested in the study but are on any of these medications/supplements at the time of intake, they will be instructed to wean the medication as appropriate (working with the prescribing MD), and they will be enrolled after a 6-week wash-out period.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (2)

Childrens National Medical Center

Washington D.C., District of Columbia, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Auld DS, Robitaille R. Glial cells and neurotransmission: an inclusive view of synaptic function. Neuron. 2003 Oct 9;40(2):389-400. doi: 10.1016/s0896-6273(03)00607-x.

  PMID: 14556716 BACKGROUND

• Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985 Mar;89(5):485-91.

  PMID: 3993694 BACKGROUND

• Barger SW, Moerman AM, Mao X. Molecular mechanisms of cytokine-induced neuroprotection: NFkappaB and neuroplasticity. Curr Pharm Des. 2005;11(8):985-98. doi: 10.2174/1381612053381594.

  PMID: 15777249 BACKGROUND

• Lane R, Kessler R, Buckley AW, Rodriguez A, Farmer C, Thurm A, Swedo S, Felt B. Evaluation of Periodic Limb Movements in Sleep and Iron Status in Children With Autism. Pediatr Neurol. 2015 Oct;53(4):343-9. doi: 10.1016/j.pediatrneurol.2015.06.014. Epub 2015 Jun 26.

  PMID: 26231264 DERIVED

• Pardo CA, Buckley A, Thurm A, Lee LC, Azhagiri A, Neville DM, Swedo SE. A pilot open-label trial of minocycline in patients with autism and regressive features. J Neurodev Disord. 2013;5(1):9. doi: 10.1186/1866-1955-5-9. Epub 2013 Apr 8.

  PMID: 23566357 DERIVED

MeSH Terms

Conditions

Autistic Disorder; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Small, uncontrolled pilot.

Results Point of Contact

• Title: Dr. Susan Swedo
• Organization: NIH/NIMH/PDN Branch

swedos@mail.nih.gov

301-496-5323

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2006
• First Posted: December 11, 2006
• Study Start: November 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: April 1, 2011
• Last Updated: December 11, 2015
• Results First Posted: December 11, 2015

Record last verified: 2015-11

Locations

US (2)