Autistic DisorderPhase 3NCT00198120
Safety and Effectiveness of D-Cycloserine in Children With Autism
A Phase 3 study testing D-cycloserine in people with Autistic Disorder, run by Indiana University at 1 site in United States.
Trial summary
This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children. Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- Autistic Disorder
- What is being tested?
- D-cycloserine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2004to Aug 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age 3 Years to 12 Years
- Diagnostic Statistical Manual Version -IV (DSM-IV) and Autism Diagnostic Interview - Revised (ADI-R)-confirmed Diagnosis of Autistic Disorder
- Aberrant Behavior Checklist (ABC) Lethargy Subscale Score of 13 or greater
Who cannot join
- Children with Severe to Profound Mental Retardation
- Weight at Screening Visit <11 kilograms
- Clinical Global Impressions-Severity Score of 7
- Presence of a Neurodevelopmental Disorder with Possible Associations to Autism: Subjects with Fragile X Syndrome, Tuberous Sclerosis, or other neurodevelopmental disorders known to be associated with autism or autistic features will be excluded.
- Presence of a Psychiatric Disorder that would Require a Specific Type of Treatment: Subjects with major depressive disorder, bipolar disorder, or a psychotic disorder will be excluded because treatment for these disorders often requires specific psychotropic agents. Subjects with an active substance use disorder will be excluded because of safety concerns and problems this would cause in assessing efficacy.
- Presence of a Medical Condition that would make Treatment with D-Cycloserine Less Safe: Subjects with significant cardiac, hepatic, or renal disease will be excluded due to concerns about pharmacokinetic alterations or adverse effects. Subjects with epilepsy or a history of seizures will be excluded due to rare reports of seizures with high doses of D-cycloserine. D-cycloserine is an U.S. FDA Pregnancy Category C drug. Because of the unknown effects of D-cycloserine on the developing human fetus, females of childbearing potential will be given a urine pregnancy test and required to use a suitable form of birth control during the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children, Christian Sarkine Autism Treatment Center
Indianapolis, Indiana, 46202
About this study
Official title: A Randomized Controlled Trial of D-Cycloserine in Autism
This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children.
Read the detailed description
This project proposes to study the efficacy and safety of D-cycloserine in children with autism. The central hypothesis of this project is that D-cycloserine will be efficacious in reducing certain symptoms of autism including some aspects of social impairment.
Autism is a severe neuropsychiatric disorder with a prevalence of at least 0.1 %. Despite investigations into the pharmacologic treatment of autism, no drugs have been shown to consistently improve the core symptoms of the disorder, namely social and communication impairment. Pilot data has suggested that D-cycloserine, a drug that affects the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, has efficacy for the symptom of social withdrawal in autism. In this study, children with autism will be randomly assigned to treatment with either D-cycloserine or placebo for 8 weeks. Both the subjects and investigators will be blind to treatment assignment. Subjects will be rated on a variety of clinical measures to examine the effects of D-cycloserine on social withdrawal and other symptoms of autism. Safety data including side-effects, vital signs, blood tests, and electrocardiograms will be performed at the beginning and end of the study. This study will provide important information about the effects of D-cycloserine for treating core and associated symptoms of autism. It will also greatly expand the knowledge about glutamatergic agents in autism and provide crucial information regarding the pathophysiology and future design of drug studies in autism.
- Conditions
- Autistic Disorder
- Being tested
- D-cycloserine, Placebo
- Keywords
- Autistic Disorder, cycloserine, pharmacology, glutamatergic agents, communication, social interaction, Double-Blind Method
- Medical subject headings
- Autistic Disorder, Communication
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-cycloserineDrug
Also called Seromycin, Cycloserine
D-Cycloserine 0.6mg/kg/day in week 1 D-Cycloserine 1.1mg/kg/day in week 2 D-Cycloserine 1.7mg/kg/day in week 3-8 Flexible dosing based on response. Capsule Strength: 10mg, 20mg
PlaceboDrug
Placebo: same dosing schedule and capsule strength
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive D-Cycloserine for 8 weeks. Receives: Drug: D-cycloserine |
| 2 | Placebo comparator | Participants will receive placebo for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Clinical Global Impressions (CGI) Global Improvement
All randomized subjects in the Double-Blind Phase will be assessed for change.
Measured: Change from Baseline at 8 Weeks
Change in Clinical Global Impressions (CGI) Global Improvement
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase
Measured: Change from Open-Label Baseline at 8 Weeks
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
All randomized subjects in the Double-Blind Phase will be assessed for change.
Measured: Change from Baseline at 8 Weeks.
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase
Measured: Change from Open-Label Baseline at 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startFeb 2004
- Primary completionSep 2007
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autistic DisorderStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Sponsor
- Investigators
- Christopher J. McDougle, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00198120
- Sponsor's protocol ID
- K23MH068627
- Other IDs
- K23MH068627, 0305-30, DDTR BK-TKND
- Status last verified
- Apr 2016
- First submitted
- 12 Sep 2005
- Last updated
- 12 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711Aye SZ, Ni H, Sein HH, Mon ST, Zheng Q, Wong YKY. The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder. Cochrane Database Syst Rev. 2021 Feb 14;2(2):CD013457. doi: 10.1002/14651858.CD013457.pub2.
PubMed 33583058
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of D-Cycloserine in Autism
- ClinicalTrials.gov ID
- NCT00198120
- Acronym / sponsor ID
- K23MH068627
- Conditions
- Autistic Disorder
- Keywords
- Autistic Disorder, cycloserine, pharmacology, glutamatergic agents, communication, social interaction, Double-Blind Method
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), National Alliance for Research on Schizophrenia and Depression
- Study start
- Feb 2004
- Primary completion
- Sep 2007 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children.
Detailed description
This project proposes to study the efficacy and safety of D-cycloserine in children with autism. The central hypothesis of this project is that D-cycloserine will be efficacious in reducing certain symptoms of autism including some aspects of social impairment.
Autism is a severe neuropsychiatric disorder with a prevalence of at least 0.1 %. Despite investigations into the pharmacologic treatment of autism, no drugs have been shown to consistently improve the core symptoms of the disorder, namely social and communication impairment. Pilot data has suggested that D-cycloserine, a drug that affects the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, has efficacy for the symptom of social withdrawal in autism. In this study, children with autism will be randomly assigned to treatment with either D-cycloserine or placebo for 8 weeks. Both the subjects and investigators will be blind to treatment assignment. Subjects will be rated on a variety of clinical measures to examine the effects of D-cycloserine on social withdrawal and other symptoms of autism. Safety data including side-effects, vital signs, blood tests, and electrocardiograms will be performed at the beginning and end of the study. This study will provide important information about the effects of D-cycloserine for treating core and associated symptoms of autism. It will also greatly expand the knowledge about glutamatergic agents in autism and provide crucial information regarding the pathophysiology and future design of drug studies in autism.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: D-cycloserineParticipants will receive D-Cycloserine for 8 weeks. |
| 2 | Placebo comparator | Drug: PlaceboParticipants will receive placebo for 8 weeks. |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Age 3 Years to 12 Years
- Diagnostic Statistical Manual Version -IV (DSM-IV) and Autism Diagnostic Interview - Revised (ADI-R)-confirmed Diagnosis of Autistic Disorder
- Aberrant Behavior Checklist (ABC) Lethargy Subscale Score of 13 or greater
Key exclusion criteria (6 listed)
- Children with Severe to Profound Mental Retardation
- Weight at Screening Visit <11 kilograms
- Clinical Global Impressions-Severity Score of 7
- Presence of a Neurodevelopmental Disorder with Possible Associations to Autism: Subjects with Fragile X Syndrome, Tuberous Sclerosis, or other neurodevelopmental disorders known to be associated with autism or autistic features will be excluded.
- Presence of a Psychiatric Disorder that would Require a Specific Type of Treatment: Subjects with major depressive disorder, bipolar disorder, or a psychotic disorder will be excluded because treatment for these disorders often requires specific psychotropic agents. Subjects with an active substance use disorder will be excluded because of safety concerns and problems this would cause in assessing efficacy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-cycloserineAlso: Seromycin, CycloserineD-Cycloserine 0.6mg/kg/day in week 1 D-Cycloserine 1.1mg/kg/day in week 2 D-Cycloserine 1.7mg/kg/day in week 3-8 Flexible dosing based on response. Capsule Strength: 10mg, 20mg | Drug | 1 |
| PlaceboPlacebo: same dosing schedule and capsule strength | Drug | 2 |
Primary outcome
Change in Clinical Global Impressions (CGI) Global Improvement
Time frame: Change from Baseline at 8 Weeks
All randomized subjects in the Double-Blind Phase will be assessed for change.
Change in Clinical Global Impressions (CGI) Global Improvement
Time frame: Change from Open-Label Baseline at 8 Weeks
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
Time frame: Change from Baseline at 8 Weeks.
All randomized subjects in the Double-Blind Phase will be assessed for change.
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
Time frame: Change from Open-Label Baseline at 8 Weeks
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2016.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
- Derived from this study: PubMed 33583058Aye SZ, Ni H, Sein HH, Mon ST, Zheng Q, Wong YKY. The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder. Cochrane Database Syst Rev. 2021 Feb 14;2(2):CD013457. doi: 10.1002/14651858.CD013457.pub2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher J. McDougle, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing D-cycloserine in people with Autistic Disorder, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Clinical Global Impressions (CGI) Global Improvement (time frame: Change from Baseline at 8 Weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00198120, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2016.