Research and Clinical Trials

The Division’s research focuses on a wide range of neurological disorders, including mitochondrial disease, movement disorders, epilepsy, Angelman’s syndrome, and cognitive impairment associated with autism spectrum disorders and genetic/metabolic disorders.

Clinical Trials

Duchenne Muscular Dystrophy

Phase 3 Clinical Trial for Eteplirsen for Boys with Duchenne Muscular Dystrophy

Eteplirsen is an experimental drug in development to treat about 13 percent of people with Duchenne muscular dystrophy, which is caused by specific mutations (flaws) in the gene for the muscle protein dystrophin. The goal of treatment with eteplirsen — known as an exon-skipping drug — is to coax muscle cells to reinterpret genetic information for the dystrophin protein so that functional dystrophin protein can be made even though the dystrophin gene is flawed.

Eligibility: Boys with Duchenne muscular dystrophy between the ages of 7 and 16

To learn more and to see if your child may quality for the study, contact Dr. Richard Haas at rhaas@rchsd.org or 858-966-6246.

Neonatal Seizures

NEOLEV2 Efficacy of Intravenous Levetiracitam in the Treatment of Neonatal Seizures / NEOLEV2

This study hopes to improve treatment of neonatal seizures in this vulnerable and under researched population. Levetiracetam (LEV or trade name Keppra) is a very promising new treatment for neonatal seizures. Current treatments are poorly effective and have significant side effects. This medicine has been used in oral form in older children for over a decade, but experience with use in babies is limited.

The study will compare effects of LEV vs phenobarbital (the traditional treatment for neonatal seizures), obtain essential safety & efficacy data, and develop remote EEG monitoring systems that will facilitate rapid seizure detection for quicker treatment.

To learn more about the study, contact Dr. Richard Haas at rhaas@rchsd.org or 858-966-8068.

Rett Syndrome

To learn more about these studies, contact Dr. Jeffrey Neul at jneul@rchsd.org.

  1. A Safety Study of NNZ-2566 in Pediatric Rett Syndrome

clinicaltrials.gov: NCT02715115

This study will investigate the safety, tolerability and blood pharmacokinetics of treatment with oral administration of NNZ-2566 at 50 mg/kg, 100 mg/kg, 200 mg/kg BID, or placebo BID, in children and adolescent females with Rett syndrome. The study also will also investigate measures of efficacy and biomarkers during treatment.

Eligibility

Ages Eligible for Study: 5 Years to 15 Years   (Child)
Genders Eligible for Study: Female
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

  • Diagnosis of classic/typical Rett syndrome with a documented mutation of the MeCP2 gene.
  • Age 5-15 years.
  • Weight at Screening and Baseline between 15.0 kg-100.0 kg (at least 15.0 kg and no greater than 100.0 kg).
  • Each subject must be able to swallow the study medication provided as a liquid solution, or via gastrostomy tube.

Exclusion Criteria:

  • Actively undergoing neurological regression
  • Abnormal QT interval, prolongation or significant cardiovascular history
  • Current treatment with insulin
  • Anti-convulsants with liver enzyme inducing effects
  • Unstable seizure profile
  • Excluded concomitant medications
  • Current clinically significant (as determined by the investigator). cardiovascular, renal, hepatic, or respiratory disease
  • Gastrointestinal disease which may interfere with the absorption, distribution, metabolism or excretion of the study medication
  • History of, or current cerebrovascular disease or brain trauma
  • History of, or current clinically significant endocrine disorder, e.g. hypo- or hyperthyroidism, or diabetes mellitus
  • History of, or current, malignancy
  • Significant hearing and/or visual impairments that may affect ability to complete the test procedures
  • Allergy to strawberry
  1. Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms

clinicaltrials.gov: NCT02790034

This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome. A third of equally randomised patients in to will be treated with 5 mg BID, another third with 10 mg BID and the remaining third with placebo BID over a course of 24 weeks.

Eligibility

Ages Eligible for Study: 13 Years and older   (Child, Adult, Senior)
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

  • Body weight ≥ 25 kg
  • Diagnostic:
    1. Diagnosis of Rett syndrome based on consensus clinical criteria (Neul et al, 2010). A test for MECP2 mutations (Xq28), will be performed at screening if results from an accredited laboratory are not available; selection for the trial is not contingent on the results of the MECP2 test. Patients with MECP2 duplications will not be eligible.
    2. One or more of the following breathing dysfunctions: periodic apnea during wakefulness, intermittent hyperventilation, breath-holding spells, air swallowing, forced expulsion of air or saliva.
    3. Patient meets all of the following criteria related to breathing abnormalities:
  • Parent report of 10 episodes or more of breathing abnormality per day during wakefulness in the week prior to the screening visit.
  • Time per hour spent on normal breathing is less than 90 percent of the total time per hour of wakefulness (i.e., ≥10% of the time should be abnormal breathing).
  • Has at least 10 episodes of breathing dysrhythmia, defined by episodes ≥10 seconds of breath holding (apnea), per hour during cardiorespiratory monitoring (performed with home/ambulatory monitoring system during screening period).

4. Stable medication regimen for four weeks prior to beginning the study (if receiving services – physical, occupational, or speech therapy – subjects must be on a stable regimen of these services for three months prior to beginning the study).

  • Procedural
    1. Parent/legal guardian/representative has provided written consent prior to the patient participating in the study. Where feasible, consent or assent for patients less than 18 years of age, has also been provided by the patient.
    2. Ability to swallow study medication provided either as capsules or combined with food/drink.
    3. Patient is cooperative, willing to complete all aspects of the study and capable of doing so with assistance of a caregiver.
    4. Caregiver is able to understand the instructions and fully participate.

Exclusion Criteria:

  • Meets any of the diagnostic exclusion criteria for Rett syndrome, Typical (Neul et al, 2010)
  • Patient is participating in a clinical trial with another investigational drug or has taken an investigational drug within one month or five half-lives (whichever is longer) prior to screening.
  • Hypersensitivity to sarizotan or other 5-HT1a agonists.
  • Current clinically significant (as determined by Investigator) cardiovascular, respiratory (e.g. severe asthma), gastrointestinal, renal, hepatic, hematologic or other medical disorders, in addition to those directly related to the patient’s Rett syndrome.
  • QTcF interval on the ECG is greater than 450 msec.
  • Surgery planned during the study (except for insertion of gastrostomy tube).
  • Severe diabetes mellitus or fatty acid oxidation disorder.
  • Ophthalmologic history including any of the following conditions: albino patients, family history of hereditary retinal disease, retinitis pigmentosa, any active retinopathy or severe diabetic retinopathy.
  • Females who are pregnant, breastfeeding, or of childbearing potential and not using a hormonal contraceptive.
  1. Natural History of Rett Syndrome & Related Disorders

clinicaltrials.gov: NCT02738281

The purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT including the range of clinical involvement and to correlate genotype-phenotype over a broad spectrum of phenotypes. While much has been learned about RTT, improvements are required in understanding the role of factors such as X chromosome inactivation, genetic background, and others including the environment, on the great variability observed even between individuals with the same MECP2 mutation. These data will be essential to the development and conduct of clinical trials that are anticipated from ongoing studies in animal models for RTT. This study will not include clinical trials, but should set the stage for such trials and other translational research projects (e.g., development of biomarkers).

 Eligibility

Ages Eligible for Study: Child, Adult, Senior
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Sampling Method: Probability Sample

Study Population

Females and males of all ages must have complete testing for MECP2, FOXG1 and CDKL5 genes mutations AND must meet these requirements:

Gene positive for a sequence mutation, duplication or deletion in one of these three genes

OR

Meet consensus criteria for Rett syndrome (typical or atypical).

Criteria

Inclusion Criteria:

  • Individuals of both genders and of all ages, with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes, or those with RTT (atypical or typical) who are mutation negative.

Exclusion Criteria:

  • Individuals who do not meet the above criteria will be excluded.
  1. Biobanking of Rett Syndrome and Related Disorders:

clinicaltrials.gov: NCT02705677

The overarching purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including CDKL5, FOXG1, and individuals with MECP2 mutations who do not have RTT. Although all these disorders are the result of specific genetic changes, there remains broad clinical variation that is not entirely accounted for by known biological factors. Additionally, clinical investigators currently do not have any biomarkers of disease status, clinical severity, or responsiveness to therapeutic intervention. To address these issues, biological materials (DNA, RNA, plasma, cell lines) will be collected from affected individuals and in some cases from unaffected family members, initial evaluation performed to identify additional biological factors contributing to disease severity, and these materials will be stored for future characterization.

Eligibility

Ages Eligible for Study: Child, Adult, Senior
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Sampling Method: Probability Sample

Study Population

Females and males of all ages must have complete testing for MECP2, FOXG1, and CDKL5 genes mutations AND must meet these requirements:

Gene positive for a sequence mutation, duplication or deletion in one of these three genes

OR

Meet consensus criteria for Rett syndrome (typical or atypical).

Criteria

Inclusion Criteria:

  • Individuals of both genders and of all ages, with RTT, MECP2 Dup, and, RTT-related disorders including those with mutations or deletions in CDKL5 and FOXG1 genes, or those with RTT (atypical or typical) who are mutation negative. Additionally, unaffected family members of those people who meet the disease specific criteria stated will eligible.

Exclusion Criteria:

  • Individuals who do not meet the above criteria will be excluded.

Tourette syndrome

T-Force Study (Not currently recruiting): The primary purpose of this study is to determine the safety and tolerability of an investigational medication for Tourette syndrome. Each child who qualifies will receive study medication, study-related medical exams and laboratory tests at no cost.

Eligibility critera: Boys and girls ages 6 to 18 with Tourette syndrome

Compensation for time and travel may be available.