Fragile X SyndromeNCT01053156

Trial of Minocycline to Treat Children With Fragile X Syndrome

A study testing minocycline hydrochloride in people with Fragile X Syndrome, run by University of California, Davis at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 42 months to 16 years
Conditions the study is for: Fragile X Syndrome
What is being tested?: minocycline hydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 66 participants
Where: 1 siteUnited States
Study dates: Jan 2010to Dec 2011
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 42 months to 16 years
All sexes
No healthy volunteers
Child

Who may be able to join

Must have fragile X syndrome with molecular documentation
Current pharmacological treatment regimen has been stable for at least 4 weeks

Who cannot join

Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study
subjects who are unable to take oral medication
subjects who have been on minocycline previously
subjects who are allergic to minocycline or tetracyclines
subjects who are pregnant
subjects with history of lupus or hepatic dysfunction

Trial locations and contacts

1 site in 1 country.

United States1 site

M.I.N.D. Institute at University of California at Davis Medical Center
Sacramento, California, 95817

Other trials in United States

About this study

Official title: Randomized Double-Blind Controlled Cross Over Trial of Minocycline in Children With Fragile X Syndrome

This is a single center study at the UC Davis MIND Institute in patients age 3.5-16 years of age with fragile X syndrome (FXS), funded by a National Fragile X Foundation Grant. It is a controlled trial of minocycline, an antibiotic commonly used in children for infection or for treatment of neurodegenerative disorders. We are investigating its use in FXS because it lowers matrix metalloproteinase 9 (MMP9) levels, which are high in FXS, and it also strengthens brain connections in the animal models of FXS. We hypothesize that minocycline will likely be helpful for language, behavior and/or cognition in fragile X patients.

Read the detailed description

The aim of this study is to carry out a double-blind placebo controlled trial of minocycline treatment in children with FXS who are 3.5 to 16 years of age. At baseline, we will assess behavior and perceptual and cognitive development. After the children have been treated for 3 months with either minocycline or placebo, they undergo the same baseline testing. They will then cross over and be treated for a second 3 months. We will carry out testing again at the end of the second 3 month period. We will also assess the side effects of minocycline treatment throughout the study.

Conditions: Fragile X Syndrome
Being tested: minocycline hydrochloride, Placebo
Keywords: Fragile X syndrome, minocycline, targeted treatment
Medical subject headings: Fragile X Syndrome, cyclopia sequence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

minocycline hydrochlorideDrug
Minocycline hydrochloride dosed orally once a day for 3 months.
PlaceboDrug
Placebo will be given daily for 3 months.

Study groups in NCT01053156
Study group	Role	What they receive
Placebo pill	Placebo comparator	All patients will be on placebo for 3 months in this crossover study. Receives: Drug: Placebo
Minocycline	Experimental	All patients will be on minocycline for 3 months in this crossover trial. Receives: Drug: minocycline hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Clinical Global Impression Scale (CGI)
The CGI-I utilizes history from primary caregivers and incorporates it into a seven step clinical rating for follow up throughout treatment, from 1 "very much improved" to 7 "very much worse". Lower scores indicate more improvement. Scores were obtained post treatments. Scores from when the patients were on minocycline either first or second were combined and averaged to determine a least squares mean and placebo scores were obtained in the same manner.
Measured: 3 months (post first treatment) and 6 months (post second treatment)
Visual Analogue Scale- Behavior 1
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the first behavior that the caregivers noted, out of three.
Measured: Baseline, 3 months, 6 months

Secondary outcomes (9)

Visual Analogue Scale- Behaviors 2
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the second behavior that the caregivers noted, out of three.
Measured: Baseline, 3 months, 6 months
Expressive Vocabulary Test-2
The EVT-2 standard score assesses language development through a participant's one word synonym response to visual stimuli. Standard scores range from 20-160. A standard score of 100 is average, with a 15 point standard deviation. Higher values represent a better outcome.
Measured: Baseline, 3 months and 6 months
Vineland Adaptive Behavior Scale-II (VABS-II)Adaptive Behavior Composite Score
The VABS-II Adaptive Behavior Composite Score was used to assess adaptive skills. An Adaptive Behavior Composite Score may range from 20-160 with an average of 100 with a standard deviation of 15. Higher scores show improvement.
Measured: Baseline, 3 months, and 6 months
Aberrant Behavior Checklist-Community Edition (ABC-C)Composite Score
The ABC-C composite scores were used to quantify the severity of a patient's behaviors. A composite score consists of subscale scores including Irritability and Agitation, Lethargy and Social Withdrawal, Stereotypic Behavior, Hyperactivity and Noncompliance, and Inappropriate Speech. The composite score may range from 0-174. Lower scores indicate improvement.
Measured: Baseline, 3 months, and 6 months
Visual Analogue Scale Behavior 3- VAS3
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the third behavior that caregivers noted, out of three.
Measured: Baseline, 3 months, 6 months
VAS Categorized by Behavior: Aggression/ ADHD
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with aggression or ADHD behaviors.
Measured: Baseline, 3 months, 6 months
VAS Categorized by Behavior:Anxiety/ Mood
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with anxiety or mood related behaviors.
Measured: Baseline, 3 months, 6 months
VAS Categorized by Behavior:Language/ Cognition
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with language or cognitive symptoms.
Measured: Baseline, 3 months, 6 months
VAS Categorized by Behavior: Other
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the least squares mean of all behaviors having to do with other behaviors that were not able to be categorized.
Measured: Baseline, 3 months, 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2010Dec 2011

First posted21 Jan 2010 (estimated)
Study startJan 2010
Primary completionDec 2011
Study completionDec 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
More trials run by University of California, DavisThe 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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 66 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01053156
Sponsor's protocol ID: 200917522
Status last verified: May 2017
First submitted: 19 Jan 2010
Last updated: 30 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet. 2009 Feb;46(2):94-102. doi: 10.1136/jmg.2008.061796. Epub 2008 Oct 3.
PubMed 18835858

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
Aggressive Behavior in Fragile X Syndome
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
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A Study to Investigate the Effects and Safety of Codabakalner for the Treatment of FXS in Male Participants and Adult Participants With ADS
Fragile X Syndrome (FXS), Autism Spectrum Disorder (ASD)

All Fragile X Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Double-Blind Controlled Cross Over Trial of Minocycline in Children With Fragile X Syndrome
ClinicalTrials.gov ID: NCT01053156
Acronym / sponsor ID: 200917522
Conditions: Fragile X Syndrome
Keywords: Fragile X syndrome, minocycline, targeted treatment
Study type: Interventional
Recruitment status: Completed
Enrolment: 66 participants (actual)
Lead sponsor: University of California, DavisUniversity, hospital or other
Collaborators: The National Fragile X Foundation
Study start: Jan 2010
Primary completion: Dec 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 21 Jan 2010 (estimated)
Results: Posted 30 Jul 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Placebo pill	Placebo comparator	Drug: PlaceboAll patients will be on placebo for 3 months in this crossover study.
Minocycline	Experimental	Drug: minocycline hydrochlorideAll patients will be on minocycline for 3 months in this crossover trial.

Who may qualify

Ages: 42 months to 16 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

Must have fragile X syndrome with molecular documentation
Current pharmacological treatment regimen has been stable for at least 4 weeks

Key exclusion criteria (6 listed)

Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study
subjects who are unable to take oral medication
subjects who have been on minocycline previously
subjects who are allergic to minocycline or tetracyclines
subjects who are pregnant

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
minocycline hydrochlorideMinocycline hydrochloride dosed orally once a day for 3 months.	Drug	Minocycline
PlaceboPlacebo will be given daily for 3 months.	Drug	Placebo pill

Primary outcome

Clinical Global Impression Scale (CGI)
Time frame: 3 months (post first treatment) and 6 months (post second treatment)
The CGI-I utilizes history from primary caregivers and incorporates it into a seven step clinical rating for follow up throughout treatment, from 1 "very much improved" to 7 "very much worse". Lower scores indicate more improvement. Scores were obtained post treatments. Scores from when the patients were on minocycline either first or second were combined and averaged to determine a least squares mean and placebo scores were obtained in the same manner.
Visual Analogue Scale- Behavior 1
Time frame: Baseline, 3 months, 6 months
A VAS is used to represent a caregiver's assessment of given behaviors, which were chosen by the parents. Caregivers marked a 10 cm horizontal line representing a visual continuum of each behavior from "worst behavior" to "behavior not a problem." Greater values indicate greater improvement. This measure represents the first behavior that the caregivers noted, out of three.

9 secondary outcomes

Visual Analogue Scale- Behaviors 2
Time frame: Baseline, 3 months, 6 months
Expressive Vocabulary Test-2
Time frame: Baseline, 3 months and 6 months
Vineland Adaptive Behavior Scale-II (VABS-II)Adaptive Behavior Composite Score
Time frame: Baseline, 3 months, and 6 months
Aberrant Behavior Checklist-Community Edition (ABC-C)Composite Score
Time frame: Baseline, 3 months, and 6 months
Visual Analogue Scale Behavior 3- VAS3
Time frame: Baseline, 3 months, 6 months
VAS Categorized by Behavior: Aggression/ ADHD
Time frame: Baseline, 3 months, 6 months
VAS Categorized by Behavior:Anxiety/ Mood
Time frame: Baseline, 3 months, 6 months
VAS Categorized by Behavior:Language/ Cognition
Time frame: Baseline, 3 months, 6 months
VAS Categorized by Behavior: Other
Time frame: Baseline, 3 months, 6 months

Results and safety

Results posted to the registry on 30 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocycline First, Then Placebo Second	33	28
Placebo First, Minocycline Second	33	27

Primary outcome: Clinical Global Impression Scale (CGI)

Time frame: 3 months (post first treatment) and 6 months (post second treatment). Least squares mean (Standard Error). Unit: units on a scale

Measure	Minocycline n = 55	Placebo n = 55
Value	2.49 (0.13)	2.97 (0.13)

Population analysed: Any participant who completed at least the first arm of the trial were included in the intention to treat analysis

Primary outcome: Visual Analogue Scale- Behavior 1

Time frame: Baseline, 3 months, 6 months. Least squares mean (Standard Error). Unit: units on a scale

Measure	Baseline n = 55	Minocycline n = 55	Placebo n = 55
Value	2.28 (0.21)	4.60 (0.31)	4.44 (0.30)

Population analysed: Any participant who completed at least the first arm of the trial were included in the intention to treat analysis

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocycline	0 of 66 (0%)	53 of 66 (80.3%)	Not reported
Placebo	1 of 66 (1.5%)	53 of 66 (80.3%)	Not reported

Limitations and caveats (from the sponsor): Results may be potentially biased by study design weaknesses, including unblinding of subjects when they completed the study, drug-related side effects unblinding and preliminary efficacy analysis results known to investigators.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 18835858Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM. Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet. 2009 Feb;46(2):94-102. doi: 10.1136/jmg.2008.061796. Epub 2008 Oct 3.

Related trials for Fragile X Syndrome

Not yet recruitingPhase 2
Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
Aggressive Behavior in Fragile X Syndome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruiting
Single Session Support for Parents of Children With Neurodevelopmental Disabilities Struggling With Anxious Avoidance
Neurodevelopmental Disorders, Autism Spectrum Disorder (ASD)
RecruitingObservational study
Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, Including, Sickle Cell Disease
Not yet recruitingPhase 2/3
A Study to Investigate the Effects and Safety of Codabakalner for the Treatment of FXS in Male Participants and Adult Participants With ADS
Fragile X Syndrome (FXS), Autism Spectrum Disorder (ASD)

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.

Randi J Hagerman, MD principal investigator

M.I.N.D. Institute at University of California at Davis, Sacramento CA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing minocycline hydrochloride in people with Fragile X Syndrome, run by University of California, Davis 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 2 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 30 May 2017. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Clinical Global Impression Scale (CGI) (time frame: 3 months (post first treatment) and 6 months (post second treatment)). The study lists 2 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 NCT01053156, which also lists 1 linked publication.

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 30 May 2017.