Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome

NCT ID: NCT03047980

Last Updated: 2021-11-01

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-31

Study Completion Date

2020-10-27

Brief Summary

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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

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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.

Conditions

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Sturge-Weber Syndrome

Keywords

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SWS Cognitive impairment sirolimus

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Sirolimus

Intervention Type DRUG

Low dose oral sirolimus

Interventions

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Sirolimus

Low dose oral sirolimus

Intervention Type DRUG

Other Intervention Names

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Rapamycin Rapamune

Eligibility Criteria

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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.).
Minimum Eligible Age

3 Years

Maximum Eligible Age

31 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Faneca 66 Foundation

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Anne Comi, MD

OTHER

Sponsor Role lead

Responsible Party

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Anne Comi, MD

Principal Investigator, Director Sturge-Weber Center, Kennedy Krieger Institute, Professor Johns Hopkins University School of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Anne M Comi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Locations

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Kennedy Krieger Institute

Baltimore, Maryland, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2U54NS065705

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BVMC6209

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB00079722

Identifier Type: -

Identifier Source: org_study_id