Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome

NCT03047980 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB000797222U54NS065705BVMC6209
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Sturge-Weber Syndrome

Keywords

SWS; Cognitive impairment; sirolimus

Outcome Measures

Primary Outcomes (1)

• Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery

  Change over six months in cognitive functioning in Sturge-Weber syndrome is the primary outcome measure. This outcome will be assessed using the NIH Toolbox Cognitive Battery, a panel of testing which includes the following measures: * the Flanker Inhibitory Control and Attention Test (executive function and attention) * the Dimensional Change Card Sort Test (executive function) * Picture Sequence Memory Test (episodic memory) * Oral Reasoning Recognition Test and Picture Vocabulary Test (language skills) * Pattern Comparison Processing Speed Test (processing speed) * List Sorting Working Memory Test (working memory) * 9-hole Peg Test (dexterity) * Grip Strength Test (grip strength) and * Patient-Reported Outcomes Measurement Information System (PROMIS) (self-report emotional functioning). These scores are rescaled to T scores (mean = 50, standard deviation (SD) = 10), referenced against the US population. Higher scores indicate better outcome. T scores only were analyzed.

  Baseline and at 6 months on the study drug

Secondary Outcomes (3)

• Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band

  Baseline and at 6months on the study drug

• Change in Sturge-Weber Syndrome Clinical Neuroscore

  Baseline and at 6 months on the study drug

• Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score

  Visits at 2 weeks (baseline) and 28 weeks (study end)

Study Arms (1)

Sirolimus

EXPERIMENTAL

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

Interventions

Sirolimus DRUG

Low dose oral sirolimus

Also known as: Rapamycin, Rapamune

Sirolimus

Eligibility Criteria

• Age: 3 Years - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female patients ages 3 to 31 years of age, inclusive.
• Cognitive impairment as defined by the following:
• SWS cognitive neuroscore of ≥ 1
• Ability to participate in direct neuropsychological and developmental testing.
• English as primary language.
• Stable anti-epileptic drugs (no changes in medications except dose for \>3 months).
• 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
• 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.
• 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.)
• Adequate liver function as shown by:
• Serum bilirubin ≤ 1.5x ULN
• ALT and AST ≤ 2.5x ULN
• Written informed consent according to local guidelines. Local guidelines for subject assent will also be followed.
• 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.

You may not qualify if:

• Allergy to sirolimus or other rapamycin analogues.
• Patients with seizures secondary to metabolic, toxic, infectious or psychogenic disorder, drug abuse or current seizures related to an acute medical illness.
• Inability to keep follow-up appointments, maintain close contact with Principal Investigators, and/or complete all necessary studies to maintain safety.
• Patients in need of immediate major surgical intervention.
• 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).
• 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.
• Known history of HIV seropositivity or known immunodeficiency. Testing is not required unless a condition is suspected.
• 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.
• Patients with an active, bleeding diathesis.
• Patients with uncontrolled hyperlipidemia: fasting serum cholesterol \> 300 mg/dL AND fasting triglycerides \> 2.5 x ULN.
• 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.
• Patients with a prior history of organ transplant.
• Patients who have received live attenuated vaccines within one week of start of sirolimus and during the pilot study.
• Patients who have a history of malignancy.
• Patients who are currently part of or have participated in any clinical investigation with an investigational drug within one month prior to enrollment.

Sponsors & Collaborators

• Anne Comi, MD: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• Pfizer: collaborator
• National Institutes of Health (NIH): collaborator
• Faneca 66 Foundation: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (2)

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Links

• Hunter Nelson Sturge-Weber Center Website

MeSH Terms

Conditions

Sturge-Weber Syndrome; Cognitive Dysfunction

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Research Assistant
• Organization: Kennedy Krieger Institute

vedmurthyp@kennedykrieger.org

443-923-9569

Study Officials

• Anne M Comi, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Director Sturge-Weber Center, Kennedy Krieger Institute, Professor Johns Hopkins University School of Medicine

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: February 9, 2017
• Study Start: January 1, 2017
• Primary Completion: June 4, 2019
• Study Completion: October 27, 2020
• Last Updated: November 1, 2021
• Results First Posted: November 1, 2021

Record last verified: 2021-09

Locations

US (2)