Fragile X SyndromeNCT00858689

Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome

A study testing Minocycline in people with Fragile X Syndrome, run by FRAXA Research Foundation at 1 site in Canada.

Completed

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

Trial summary

Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment, developmental disability and autism. Minocycline is an antibiotic that has recently been used to treat the mouse model for Fragile X, and was found to reverse the structural abnormalities that are seen their brain cells. Read more about this study

Who is it for?: Ages 13 to 35 yearsHealthy volunteers can take part
Conditions the study is for: Fragile X Syndrome
What is being tested?: Minocycline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteCanada
Study dates: Oct 2007to Jan 2009
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 13 to 35 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Diagnosis of FXS by clinical evaluation and confirmed by FMR1-DNA testing with presence of full mutation or mosaicism for the full mutation. Prior DNA testing reports will be accepted, when available.
Age between 13 to 35 years inclusive at the time of informed consent.
Male or female
CGI-Severity Score of 4 or greater, indicative of moderate or greater severity of behavioural problems. This is a 7-point scale of clinical global impression of severity that the clinician fills out after considering all the available information on the patient, including the parent history, the examination in clinic, reports from the school and other sources.
Score of 9 or greater on the Aberrant Behaviour Checklist - Irritability Scale (top 50th %-tile). The ABC is a global behaviour checklist implemented for the measurement of drug and other treatment effects in mentally impaired individuals. It is made up of 5 empirically derived dimensions including irritability, lethargy/withdrawal, inappropriate speech, hyperactivity, and stereotypic behaviour based on 58 items that describe various behavioural problems.
Availability of parent and/or caregiver for all clinic visits and assessments.
English language fluency and reading level of 6th grade or greater in one caregiver.

Who cannot join

Allergy to minocycline.
Kidney disease or elevated renal function tests.
Liver disease or elevated liver function tests.
Participants with neutropenia, anemia, or thrombocytopenia.
History of systemic lupus erythematosus or screening anti-nuclear antibody (ANA) titre of >1:40, as minocycline may cause a lupus-like reaction.
Individuals who do not have a mother or caregiver who is willing to participate in the clinic visits.

Show all 10Show fewer

Individuals who are pregnant or at risk to become pregnant, specifically sexually active females will be excluded.
Presence of persistent psychotic symptoms
Subjects with symptom severity likely judged to endanger personal safety or safety of others.
History of systemic lupus erythematosus or screening anti-nuclear antibody (ANA) titre of >1:40, as minocycline may cause a lupus-like reaction.

Trial locations and contacts

1 site in 1 country.

Canada1 site

Surrey Place Centre
Toronto, Ontario, M5S 2C2

Other trials in Canada

About this study

Official title: Add-on Pilot Trial of Minocycline in Fragile X Syndrome

Read the detailed description

Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment and is also associated with a range of learning disabilities, neurological problems, such as seizures, and behavioural difficulties. For many individuals with FXS, behavioral difficulties result in severe problems within the family and community, particularly in the form of agitation, temper outbursts, hyperactivity, and aggression. These problems often require a variety of psychopharmacological and behavioural approaches. Although a variety of medications can be helpful in FXS there are no targeted interventions based on molecular abnormalities that have been studied. Defects in dendritic spine formation have been found in the brains of patients with Fragile X, suggesting these structures may represent an anatomical and physiological basis for the cognitive deficits associated with this disorder. Recent research has suggested that minocycline may have a specific benefit in the treatment of FXS. Minocycline is an antibiotic that has been found to inhibit the activity of matrix metallo-proteinase-9 (MMP-9), which is up-regulated in the hippocampus of FMR1 KO (Fragile X Mental Retardation-1 Knockout) mice and may be responsible for the immature dendritic spine profile of hippocampal neurons. Minocycline has recently been used to treat the FXS KO mouse model for Fragile X, and was found to rescue this abnormal phenotype by inducing the formation of mature dendritic spines in FMR1 KO hippocampal neurons, both in vitro and in vivo. Minocycline treated FXS KO mice also performed significantly better in the elevated maze, a cognitive performance test that measures activity and anxiety.

Exciting preclinical effects of minocycline with regard to the FXS disease model have led to this pilot proposal, which is designed to generate preliminary data that could be used to support a larger clinical trial.

The overall hypothesis is that minocycline is a specific molecular targeted treatment for FXS that will display beneficial effects on disruptive behaviour and possibly other associated features of FXS via a reduction in MMP-9 activity.

Conditions: Fragile X Syndrome
Being tested: Minocycline
Keywords: Clinical Drug Trial
Medical subject headings: Fragile X Syndrome

What participants receive

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

MinocyclineDrug
Also called Solodyn, Dynacin, Arestin, Minocin
50-100 mg PO BID for 8 weeks with an option for a 1 year extension.

Study groups in NCT00858689
Study group	Role	What they receive
minocyline 50 mg or 100 mg PO BID	Experimental	open label treatment with minocycline low or high dose, 50 mg or 100 mg PO (by mouth) BID (twice a day), added to existing medication regimen for 8 weeks Receives: Drug: Minocycline

What is being measured

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

Change From Baseline of ABC Irritability Subtest Score at 8 Weeks
The 15-item Irritability Scale includes questions about aggression, self-injury, tantrums, agitation, and unstable mood on a scale of 0 to 45 with higher scores indicating greater severity. This scale has been successfully used in previous medication studies in children with autism and in patients with FXS and in a controlled trial of ampakine CX516 in FXS. All ABC subscales showed good reliability when used by parents and caregivers of individuals with FXS to assess behavior in the CX516 study NCT00054730, and yielded intraclass correlation coefficient (ICC) values of 0.7-0.9.
Measured: Baseline and 8 weeks
ABC Irritability Subtest Score
ABC Irritability subtest score was used
Measured: 8 weeks
ABC Irritability Subtest Score
ABC (Aberrant behavior checklist) Irritability subtest score was used
Measured: 1 year

Secondary outcomes (20)

Parent Defined Target Symptoms Scale-Visual
Measured: Baseline
Clinical Global Impression Scale
Measured: Baseline
Stanford Binet 5 (SB5)
Measured: Baseline
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Measured: Baseline
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Measured: Baseline
Non-Verbal Associative Learning Task (NVALT)
Measured: Baseline
Vineland Adaptive Behaviour Scales (VABS)
Measured: Baseline
Parent Defined Target Symptoms Scale-Visual
Measured: 8 weeks
Parent Defined Target Symptoms Scale-Visual
Measured: 1 year
Clinical Global Impression Scale
Measured: 8 weeks
Clinical Global Impression Scale
Measured: 1 year
Stanford Binet 5 (SB5)
Measured: 1 year
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Measured: 8 weeks
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Measured: 1 year
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Measured: 8 weeks
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Measured: 1 year
Non-Verbal Associative Learning Task (NVALT)
Measured: 8 weeks
Non-Verbal Associative Learning Task (NVALT)
Measured: 1 year
Vineland Adaptive Behaviour Scales (VABS)
Measured: 8 weeks
Vineland Adaptive Behaviour Scales (VABS)
Measured: 1 year

Timeline

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

Oct 2007Jan 2009

First posted10 Mar 2009 (estimated)
Study startOct 2007
Primary completionNov 2008
Study completionJan 2009

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.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00858689
Sponsor's protocol ID: 010308
Status last verified: Feb 2016
First submitted: 9 Mar 2009
Last updated: 18 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol. 2010 Oct 11;10:91. doi: 10.1186/1471-2377-10-91.
PubMed 20937127

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

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)

All Fragile X Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Add-on Pilot Trial of Minocycline in Fragile X Syndrome
ClinicalTrials.gov ID: NCT00858689
Acronym / sponsor ID: 010308
Conditions: Fragile X Syndrome
Keywords: Clinical Drug Trial
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: FRAXA Research FoundationUniversity, hospital or other
Collaborators: Fragile X Research Foundation of Canada
Study start: Oct 2007
Primary completion: Nov 2008 (actual)
Study completion: Jan 2009 (actual)
First posted: 10 Mar 2009 (estimated)
Results: Posted 18 Feb 2016

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
minocyline 50 mg or 100 mg PO BID	Experimental	Drug: Minocyclineopen label treatment with minocycline low or high dose, 50 mg or 100 mg PO (by mouth) BID (twice a day), added to existing medication regimen for 8 weeks

Who may qualify

Ages: 13 to 35 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

Diagnosis of FXS by clinical evaluation and confirmed by FMR1-DNA testing with presence of full mutation or mosaicism for the full mutation. Prior DNA testing reports will be accepted, when available.
Age between 13 to 35 years inclusive at the time of informed consent.
Male or female
CGI-Severity Score of 4 or greater, indicative of moderate or greater severity of behavioural problems. This is a 7-point scale of clinical global impression of severity that the clinician fills out after considering all the available information on the patient, including the parent history, the examination in clinic, reports from the school and other sources.
Score of 9 or greater on the Aberrant Behaviour Checklist - Irritability Scale (top 50th %-tile). The ABC is a global behaviour checklist implemented for the measurement of drug and other treatment effects in mentally impaired individuals. It is made up of 5 empirically derived dimensions including irritability, lethargy/withdrawal, inappropriate speech, hyperactivity, and stereotypic behaviour based on 58 items that describe various behavioural problems.

Key exclusion criteria (10 listed)

Allergy to minocycline.
Kidney disease or elevated renal function tests.
Liver disease or elevated liver function tests.
Participants with neutropenia, anemia, or thrombocytopenia.
History of systemic lupus erythematosus or screening anti-nuclear antibody (ANA) titre of >1:40, as minocycline may cause a lupus-like reaction.

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
MinocyclineAlso: Solodyn, Dynacin, Arestin, Minocin50-100 mg PO BID for 8 weeks with an option for a 1 year extension.	Drug	minocyline 50 mg or 100 mg PO BID

Primary outcome

Change From Baseline of ABC Irritability Subtest Score at 8 Weeks
Time frame: Baseline and 8 weeks
The 15-item Irritability Scale includes questions about aggression, self-injury, tantrums, agitation, and unstable mood on a scale of 0 to 45 with higher scores indicating greater severity. This scale has been successfully used in previous medication studies in children with autism and in patients with FXS and in a controlled trial of ampakine CX516 in FXS. All ABC subscales showed good reliability when used by parents and caregivers of individuals with FXS to assess behavior in the CX516 study NCT00054730, and yielded intraclass correlation coefficient (ICC) values of 0.7-0.9.
ABC Irritability Subtest Score
Time frame: 8 weeks
ABC Irritability subtest score was used
ABC Irritability Subtest Score
Time frame: 1 year
ABC (Aberrant behavior checklist) Irritability subtest score was used

20 secondary outcomes

Parent Defined Target Symptoms Scale-Visual
Time frame: Baseline
Clinical Global Impression Scale
Time frame: Baseline
Stanford Binet 5 (SB5)
Time frame: Baseline
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time frame: Baseline
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: Baseline
Non-Verbal Associative Learning Task (NVALT)
Time frame: Baseline
Vineland Adaptive Behaviour Scales (VABS)
Time frame: Baseline
Parent Defined Target Symptoms Scale-Visual
Time frame: 8 weeks
Parent Defined Target Symptoms Scale-Visual
Time frame: 1 year
Clinical Global Impression Scale
Time frame: 8 weeks
Clinical Global Impression Scale
Time frame: 1 year
Stanford Binet 5 (SB5)
Time frame: 1 year
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time frame: 8 weeks
The Peabody Picture Vocabulary Test Third Edition (PPVT-III)
Time frame: 1 year
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: 8 weeks
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: 1 year
Non-Verbal Associative Learning Task (NVALT)
Time frame: 8 weeks
Non-Verbal Associative Learning Task (NVALT)
Time frame: 1 year
Vineland Adaptive Behaviour Scales (VABS)
Time frame: 8 weeks
Vineland Adaptive Behaviour Scales (VABS)
Time frame: 1 year

Results and safety

Results posted to the registry on 18 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocyline 50 mg or 100 mg PO BID	20	19

Primary outcome: Change From Baseline of ABC Irritability Subtest Score at 8 Weeks

Time frame: Baseline and 8 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Minocyline 50 mg or 100 mg PO BID n = 19
Value	-14.37 (7.84)

Population analysed: ABC-I change in subjects completing 8 weeks of minocycline treatment

Primary outcome: ABC Irritability Subtest Score

Time frame: 8 weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	Minocyline 50 mg or 100 mg PO BID n = 19
Value	7.74 (4.82)

Population analysed: completed 8 weeks of minocycline treatment

Primary outcome: ABC Irritability Subtest Score

Time frame: 1 year

The sponsor has not posted figures for this outcome.

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocyline 50 mg or 100 mg PO BID	0 of 20 (0%)	2 of 20 (10%)	Not reported

Limitations and caveats (from the sponsor): This was an open-label trial. Further study in a randomized controlled trial is warranted.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 20937127Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol. 2010 Oct 11;10:91. doi: 10.1186/1471-2377-10-91.
The Fragile X Research Foundation of Canada is a non-profit organization which is dedicated to funding biomedical research for improved treatment and, ultimately, a cure for fragile X.Link provided by the sponsor.
FRAXA is a non-profit organization whose mission is to accelerate progress toward effective treatments and a cure for Fragile X, by funding the most promising research.Link provided by the sponsor.

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.

Carlo Paribello, M.D. principal investigator

Fragile X Research Foundation of Canada

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 in people with Fragile X Syndrome, run by FRAXA Research Foundation at 1 site in Canada.

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 7 inclusion and 10 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 18 Feb 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 Canada. 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. 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 18 Feb 2016). 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?

Change From Baseline of ABC Irritability Subtest Score at 8 Weeks (time frame: Baseline and 8 weeks). The study lists 3 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 NCT00858689, 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 18 Feb 2016.