Sturge-Weber SyndromePhase 2/3NCT03047980
Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
A Phase 2/3 study testing Sirolimus in people with Sturge-Weber Syndrome, run by Anne Comi, MD at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 31 years
- Conditions the study is for
- Sturge-Weber Syndrome
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2017to 27 Oct 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 31 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
- Patients being treated with felbamate, unless treatment has been continuous for ≥ one year.
- 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.).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
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.
Read the 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.
- Conditions
- Sturge-Weber Syndrome
- Being tested
- Sirolimus
- Keywords
- SWS, Cognitive impairment, sirolimus
- Medical subject headings
- Sturge-Weber Syndrome, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin, Rapamune
Low dose oral sirolimus
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and at 6 months on the study drug
Secondary outcomes (3)
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band
Change in mean laterality score (by qEEG power analysis) was done comparing hemispheres and occipital lobes in the following frequency bands; delta, theta, alpha, beta, as previously described. As post-hoc analysis, baseline and follow-up qEEG of patients with and without stroke-like episodes were compared. Greater asymmetry with decreased power on the affected side is worse. We calculated a mean Laterality Score (LSb) for each band, averaged over 30 epochs and included channel pairs. Laterality Scores less than zero indicate lower power on the side ipsilateral to the port wine birthmark. In subjects who had a bilateral port wine birthmark, the side of maximal involvement was used (or the side of known involvement by MRI findings, where present).
Measured: Baseline and at 6months on the study drug
Change in Sturge-Weber Syndrome Clinical Neuroscore
Change in clinical neuroscore over the course of the study were measured. The neuroscore is comprised of frequency of seizures (0-4) , extent of hemiparesis (0-4), assessment of visual field cut (0-2) , and degree of cognitive functioning (0-5) with a minimum total score of 0 and a maximum total score of 15. Higher scores mean worsening of symptoms.
Measured: Baseline and at 6 months on the study drug
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score
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.
Measured: Visits at 2 weeks (baseline) and 28 weeks (study end)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study startJan 2017
- Primary completion4 Jun 2019
- Study completion27 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sturge-Weber SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anne Comi, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, Pfizer, National Institutes of Health (NIH), Faneca 66 Foundation, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor-investigator, Anne Comi, MD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Investigators
- Anne M Comi, M.D., Principal investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03047980
- Sponsor's protocol ID
- IRB00079722
- Other IDs
- 2U54NS065705, BVMC6209
- Status last verified
- Sep 2021
- First submitted
- 2 Feb 2017
- Last updated
- 1 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
- ClinicalTrials.gov ID
- NCT03047980
- Acronym / sponsor ID
- IRB00079722
- Conditions
- Sturge-Weber Syndrome
- Keywords
- SWS, Cognitive impairment, sirolimus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Anne Comi, MDUniversity, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, Pfizer, National Institutes of Health (NIH), Faneca 66 Foundation, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2017
- Primary completion
- 4 Jun 2019 (actual)
- Study completion
- 27 Oct 2020 (actual)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Posted 1 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusAll 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. |
Who may qualify
- Ages
- 3 to 31 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (17 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: Rapamycin, RapamuneLow dose oral sirolimus | Drug | Sirolimus |
Primary outcome
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery
Time frame: Baseline and at 6 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 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.
3 secondary outcomes
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band
Time frame: Baseline and at 6months on the study drug
Change in Sturge-Weber Syndrome Clinical Neuroscore
Time frame: Baseline and at 6 months on the study drug
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score
Time frame: Visits at 2 weeks (baseline) and 28 weeks (study end)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Hunter Nelson Sturge-Weber Center WebsiteLink provided by the sponsor.
Related trials for Sturge-Weber Syndrome
RecruitingPhase 2
Epidiolex Trial for Presymptomatic Treatment of Sturge-Weber Syndrome
Sturge - Weber Syndrome (SWS)
Not yet recruitingObservational study
Neurocutaneous Syndromes in Children: Prevalence and Clinical Characteristics
Sturge-Weber Syndrome, Neurocutaneous Syndromes
RecruitingPhase 3
A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
Venous Malformations, Lymphatic Malformations
RecruitingObservational study
Lymphatic Anomalies Registry for the Assessment of Outcome Data
Lymphatic Malformation, Generalized Lymphatic Anomaly (GLA)
RecruitingPhase 2
A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)
PIK3CA-Related Overgrowth Spectrum (PROS), Lymphatic Malformations
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne M Comi, M.D. principal investigator
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sirolimus in people with Sturge-Weber Syndrome, run by Anne Comi, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery (time frame: Baseline and at 6 months on the study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.