Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03047980
Recruitment Status : Active, not recruiting
First Posted : February 9, 2017
Last Update Posted : July 24, 2019
Sponsor:
Collaborators:
Children's Hospital Medical Center, Cincinnati
Pfizer
National Institutes of Health (NIH)
Faneca 66 Foundation
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Brief Summary:
The purpose of this research study is to gain a preliminary understanding of the safety of sirolimus in Sturge-Weber syndrome (SWS) and determine best outcomes to be used to assess the utility of sirolimus for the treatment of cognitive impairments related to Sturge-Weber syndrome.

Condition or disease Intervention/treatment Phase
Sturge-Weber Syndrome Drug: Sirolimus Phase 2 Phase 3

Detailed Description:
Sirolimus will be administered as an adjunct to all current medications. The impact of sirolimus upon cognitive functioning in Sturge-Weber syndrome is the primary outcome measure. This outcome will be assessed using a panel of testing selected based upon extensive experience in testing cognitive function in adults and children with SWS at the Kennedy Krieger Sturge-Weber Center. Changes in a quantitative EEG before and after the trial, Sturge-Weber syndrome clinical neuroscore, port-wine birthmark score, and the impact of sirolimus upon seizures will be assessed.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
Study Start Date : January 2017
Actual Primary Completion Date : June 4, 2019
Estimated Study Completion Date : September 1, 2020


Arm Intervention/treatment
Experimental: Sirolimus
All subjects will receive the sirolimus oral solution to be taken at home twice daily and will be treated on an outpatient basis. The drug will be taken for six months.
Drug: Sirolimus
Low dose oral sirolimus
Other Names:
  • Rapamycin
  • Rapamune




Primary Outcome Measures :
  1. Cognitive impairments [ Time Frame: Baseline and after six months on the study drug ]
    Change over six months in cognitive functioning in Sturge-Weber syndrome is the primary outcome measure. This outcome will be assessed using a panel of testing selected based upon extensive experience in testing cognitive function in adults and children with SWS at the Kennedy Krieger Sturge-Weber Center. These will include the measures from the National Institute of Health Toolbox.


Secondary Outcome Measures :
  1. Change in quantitative EEG [ Time Frame: Baseline and after six months on the study drug ]
    Changes in qEEG results over the course of the study

  2. Sturge-Weber syndrome clinical neuroscore [ Time Frame: First visit (0 weeks), 2 weeks, 4 weeks, 8 weeks, 16 weeks and 28 weeks (study end) ]
    Changes in clinical neuroscore over the course of the study

  3. Sturge-Weber syndrome birthmark score [ Time Frame: Visits at 2 weeks (baseline) and 28 weeks (study end) ]
    Frontal and profile photograph will be taken under standardized conditions with scoring of the port-wine birthmark for percent of face covered, thickness of birthmark, and darkness of birthmark color.

  4. Impact on sirolimus on seizures [ Time Frame: First visit (0 weeks), 2 weeks, 4 weeks, 8 weeks, 16 weeks and 28 weeks (study end) ]

    Another secondary outcome measure will be an assessment of impact upon seizures. Parents/caregivers will report the following before starting study drug and at each visit:

    • Number of seizures (specifically motor seizures)
    • Seizure duration
    • Seizure Type
    • Number of episodes of status epilepticus, defined as generalized convulsive seizure lasting longer than 10 minutes
    • Number of uses of rescue medication
    • Number of ER visits/ hospitalizations for seizures



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 31 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients ages 3 to 31 years of age, inclusive.
  2. Cognitive impairment as defined by the following:

    SWS cognitive neuroscore of ≥ 1

  3. Ability to participate in direct neuropsychological and developmental testing.
  4. English as primary language.
  5. Stable anti-epileptic drugs (no changes in medications except dose for >3 months).
  6. Adequate renal function. GFR must be greater than 50 ml/min/m2 as determined by the Schwartz Formula for children and MDRD for adults: http://www.nkdep.nih.gov/professionals/gfr_calculators/index.htm
  7. If female and of child bearing potential, documentation of a negative pregnancy test prior to enrollment determined by a urine test is required. Sexually active pre-menopausal female patients (and female partners of male patients) must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on the study drug. Abstinence will be considered an adequate contraceptive measure.
  8. INR ≤1.5 (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks.)
  9. Adequate liver function as shown by:

    • Serum bilirubin ≤ 1.5x ULN
    • ALT and AST ≤ 2.5x ULN
  10. Written informed consent according to local guidelines. Local guidelines for subject assent will also be followed.
  11. Stable dose of medications affecting the cytochrome P 450 3A4 (CYP3A4) and p glycoprotein (P gp) systems for at least 3 months prior to consent.

Exclusion Criteria:

  1. Allergy to sirolimus or other rapamycin analogues.
  2. Patients with seizures secondary to metabolic, toxic, infectious or psychogenic disorder, drug abuse or current seizures related to an acute medical illness.
  3. Inability to keep follow-up appointments, maintain close contact with Principal Investigators, and/or complete all necessary studies to maintain safety.
  4. Patients in need of immediate major surgical intervention.
  5. Concurrent severe and/or uncontrolled medical disease, which could compromise participation in the pilot study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, impaired or restrictive pulmonary function, pneumonitis or pulmonary infiltrates).
  6. Chronic treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. Inhaled steroids are allowed.
  7. Known history of HIV seropositivity or known immunodeficiency. Testing is not required unless a condition is suspected.
  8. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sirolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A gastric tube or nasogastric tube is allowed.
  9. Patients with an active, bleeding diathesis.
  10. Patients with uncontrolled hyperlipidemia: fasting serum cholesterol > 300 mg/dL AND fasting triglycerides > 2.5 x ULN.
  11. Patients who have had a major surgery or significant traumatic injury within four weeks of study entry. Patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the pilot study.
  12. Patients with a prior history of organ transplant.
  13. Patients who have received live attenuated vaccines within one week of start of sirolimus and during the pilot study.
  14. Patients who have a history of malignancy.
  15. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within one month prior to enrollment.
  16. Patients being treated with felbamate, unless treatment has been continuous for ≥ one year.
  17. Patients currently receiving anticancer therapies or who have received anticancer therapies within four weeks of study entry (including chemotherapy, radiation therapy, antibody based therapy, etc.).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03047980


Locations
Layout table for location information
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Anne Comi, MD
Children's Hospital Medical Center, Cincinnati
Pfizer
National Institutes of Health (NIH)
Faneca 66 Foundation
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Anne M Comi, M.D. Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Additional Information:
Layout table for additonal information
Responsible Party: Anne Comi, MD, Principal Investigator, Director Sturge-Weber Center, Kennedy Krieger Institute, Professor Johns Hopkins University School of Medicine, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT03047980     History of Changes
Other Study ID Numbers: IRB00079722
2U54NS065705 ( U.S. NIH Grant/Contract )
BVMC6209 ( Other Grant/Funding Number: Rare Diseases Clinical Research Network )
First Posted: February 9, 2017    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Keywords provided by Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:
SWS
Cognitive impairment
sirolimus
Additional relevant MeSH terms:
Layout table for MeSH terms
Sturge-Weber Syndrome
Brain Stem Infarctions
Klippel-Trenaunay-Weber Syndrome
Syndrome
Cognitive Dysfunction
Disease
Pathologic Processes
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Stroke
Vascular Diseases
Cardiovascular Diseases
Angiomatosis
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Neurocutaneous Syndromes
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic