Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome

NCT03047980

Last updated date
Study Location
Kennedy Krieger Institute
Baltimore, Maryland, 21205, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Sturge-Weber Syndrome
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
3-31 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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.).

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Sturge-Weber SyndromeTrial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
NCT03047980
  1. Baltimore, Maryland
  2. Cincinnati, Ohio
ALL GENDERS
3 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
Official Title  ICMJE Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sturge-Weber Syndrome
Intervention  ICMJE Drug: Sirolimus
Low dose oral sirolimus
Other Names:
  • Rapamycin
  • Rapamune
Study Arms  ICMJE 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.
Intervention: Drug: Sirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 6, 2017)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2020
Actual Primary Completion Date June 4, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.).
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 3 Years to 31 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03047980
Other Study ID Numbers  ICMJE IRB00079722
2U54NS065705 ( U.S. NIH Grant/Contract )
BVMC6209 ( Other Grant/Funding Number: Rare Diseases Clinical Research Network )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Study Sponsor  ICMJE Anne Comi, MD
Collaborators  ICMJE
  • Children's Hospital Medical Center, Cincinnati
  • Pfizer
  • National Institutes of Health (NIH)
  • Faneca 66 Foundation
  • National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator:Anne M Comi, M.D.Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
PRS Account Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP