Rett SyndromePhase 2NCT00990691
Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
A Phase 2 study testing Administration of a high dose of desipramine and Administration of a low dose of desipramine in people with Rett Syndrome, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment. Read more about this study
- Who is it for?
- Ages 4 to 18 years, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Administration of a high dose of desipramine and Administration of a low dose of desipramine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteFrance
- Study dates
- 17 Feb 2009to 21 Aug 2017
- Phase
- Phase 2
- 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 4 to 18 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Rett syndrome;
- Girls weighing less than 60 kg;
- Respiratory alteration;
- Diagnosis of Rett syndrome confirmed by MECP2 genotyping (Xq28).
Who cannot join
- Boys;
- Pregnancy and breath feeding;
- Case history of status epilepticus;
- Patient treated by IMAO or sultopride;
- Hepatic or renal failure.
Trial locations and contacts
1 site in 1 country.
About this study
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
Read the detailed description
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. The diagnosis of Rett syndrome is based on consensus clinical criteria. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
Only a few improved cases have been reported concerning buspirone (Andaku, 2005, 1 patient), topiramate (Goyal, 2004, 8 patients), diazepam (Kurihara, 2001, 1 patient) and carnitin (Plochl, 2004, 1 patient).
Only one randomized study versus placebo has been published about a treatment by naltrexone including 25 patients. A light improvement of respiratory parameters was then observed with a deterioration of the cognitive function (Percy, 2004).
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
- Conditions
- Rett Syndrome
- Being tested
- Administration of a high dose of desipramine, Administration of a low dose of desipramine, Administration of a placebo
- Keywords
- Rett syndrome
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of a high dose of desipramineDrug
Administration of a daily dose of desipramine correlated with the patient's weight :
- From 15 to 25 kg : 50 mg ;
- From 26 to 35 kg : 75 mg ;
- From 36 to 45 kg : 100 mg ;
- > 46 kg : 150 mg.
Administration of a low dose of desipramineDrug
Administration of a daily dose of desipramine correlated with the patient's weight :
- From 15 to 25 kg : 25 mg ;
- From 26 to 35 kg : 50 mg ;
- From 36 to 45 kg : 75 mg ;
- > 46 kg : 100 mg.
Administration of a placeboDrug
Administration of a daily dose of placebo
| Study group | Role | What they receive |
|---|---|---|
| Desipramine high dose | Experimental | 12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :
* From 15 to 25 kg : 50 mg ;
* From 26 to 35 kg : 75 mg ;
* From 36 to 45 kg : 100 mg ;
* > 46 kg : 150 mg. Receives: Drug: Administration of a high dose of desipramine |
| Desipramine low dose | Experimental | 12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight :
* From 15 to 25 kg : 25 mg ;
* From 26 to 35 kg : 50 mg ;
* From 36 to 45 kg : 75 mg ;
* > 46 kg : 100 mg. Receives: Drug: Administration of a low dose of desipramine |
| Placebo | Placebo comparator | 12 patients with Rett syndrome receiving a daily dose of placebo. Receives: Drug: Administration of a placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the efficacy of the desipramine on the respiratory disturbations
Measured: 2 years
Secondary outcomes (1)
To study the safety of the desipramine in the studied population
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2009 (estimated)
- Study start17 Feb 2009
- Primary completion11 Aug 2014
- Study completion21 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Josette Mancini, Principal investigator, Assistance Publique Hopitaux De Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00990691
- Sponsor's protocol ID
- 2007-37
- Other IDs
- 2007-006739-30
- Status last verified
- Jul 2018
- First submitted
- 6 Oct 2009
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Mancini J, Dubus JC, Jouve E, Roux JC, Franco P, Lagrue E, Castelnau P, Cances C, Chaix Y, Rougeot-Jung C, Cornu C, Desportes V, Vallee L, Bahi-Buisson N, Truillet R, Attolini L, Villard L, Blin O, Micallef J. Effect of desipramine on patients with breathing disorders in RETT syndrome. Ann Clin Transl Neurol. 2017 Dec 27;5(2):118-127. doi: 10.1002/acn3.468. eCollection 2018 Feb.
PubMed 29468173
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Effects of the Desipramine on the Neurovegetative Parameters of the Child With Rett Syndrome
- ClinicalTrials.gov ID
- NCT00990691
- Acronym / sponsor ID
- 2007-37
- Conditions
- Rett Syndrome
- Keywords
- Rett syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 17 Feb 2009 (actual)
- Primary completion
- 11 Aug 2014 (actual)
- Study completion
- 21 Aug 2017 (actual)
- First posted
- 7 Oct 2009 (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.
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
Detailed description
Rett syndrome is a neurodevelopmental disorder characterized by cognitive impairment, communication dysfunction, stereotypic movement disorder, and growth failure. The diagnosis of Rett syndrome is based on consensus clinical criteria. Rett syndrome is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment.
Only a few improved cases have been reported concerning buspirone (Andaku, 2005, 1 patient), topiramate (Goyal, 2004, 8 patients), diazepam (Kurihara, 2001, 1 patient) and carnitin (Plochl, 2004, 1 patient).
Only one randomized study versus placebo has been published about a treatment by naltrexone including 25 patients. A light improvement of respiratory parameters was then observed with a deterioration of the cognitive function (Percy, 2004).
A mouse experimental model of Rett syndrome created by genetic invalidation of the MECP2 gene is available. It had been then observed that adult MECP2-deficient mice show respiratory alterations and found that endogenous noradrenaline helps to maintain a normal respiratory rhythm. Desipramine, a selective inhibitor of norepinephrine reuptake, seems to be efficient to reduce the respiratory alteration occuring in MECP2-deficient mice (Insem patent 2005, Villard and Roux 2006).
The aim of the study is to evaluate these obtained results in MECP2-deficient mice on patients with Rett syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Desipramine high dose | Experimental | Drug: Administration of a high dose of desipramine12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight : * From 15 to 25 kg : 50 mg ; * From 26 to 35 kg : 75 mg ; * From 36 to 45 kg : 100 mg ; * > 46 kg : 150 mg. |
| Desipramine low dose | Experimental | Drug: Administration of a low dose of desipramine12 patients with Rett syndrome receiving a daily dose of desipramine correlated with the weight : * From 15 to 25 kg : 25 mg ; * From 26 to 35 kg : 50 mg ; * From 36 to 45 kg : 75 mg ; * > 46 kg : 100 mg. |
| Placebo | Placebo comparator | Drug: Administration of a placebo12 patients with Rett syndrome receiving a daily dose of placebo. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Rett syndrome;
- Girls weighing less than 60 kg;
- Respiratory alteration;
- Diagnosis of Rett syndrome confirmed by MECP2 genotyping (Xq28).
Key exclusion criteria (5 listed)
- Boys;
- Pregnancy and breath feeding;
- Case history of status epilepticus;
- Patient treated by IMAO or sultopride;
- Hepatic or renal failure.
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 |
|---|---|---|
| Administration of a high dose of desipramineAdministration of a daily dose of desipramine correlated with the patient's weight : * From 15 to 25 kg : 50 mg ; * From 26 to 35 kg : 75 mg ; * From 36 to 45 kg : 100 mg ; * > 46 kg : 150 mg. | Drug | Desipramine high dose |
| Administration of a low dose of desipramineAdministration of a daily dose of desipramine correlated with the patient's weight : * From 15 to 25 kg : 25 mg ; * From 26 to 35 kg : 50 mg ; * From 36 to 45 kg : 75 mg ; * > 46 kg : 100 mg. | Drug | Desipramine low dose |
| Administration of a placeboAdministration of a daily dose of placebo | Drug | Placebo |
Primary outcome
To study the efficacy of the desipramine on the respiratory disturbations
Time frame: 2 years
1 secondary outcome
To study the safety of the desipramine in the studied population
Time frame: 2 years
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 26 Jul 2018.
- Derived from this study: PubMed 29468173Mancini J, Dubus JC, Jouve E, Roux JC, Franco P, Lagrue E, Castelnau P, Cances C, Chaix Y, Rougeot-Jung C, Cornu C, Desportes V, Vallee L, Bahi-Buisson N, Truillet R, Attolini L, Villard L, Blin O, Micallef J. Effect of desipramine on patients with breathing disorders in RETT syndrome. Ann Clin Transl Neurol. 2017 Dec 27;5(2):118-127. doi: 10.1002/acn3.468. eCollection 2018 Feb.
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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.
Josette Mancini principal investigator
Assistance Publique Hopitaux De Marseille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Administration of a high dose of desipramine and Administration of a low dose of desipramine in people with Rett Syndrome, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
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 4 inclusion and 5 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 26 Jul 2018. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
To study the efficacy of the desipramine on the respiratory disturbations (time frame: 2 years). 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 NCT00990691, 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 26 Jul 2018.