Trial Outcomes & Findings for Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome (NCT NCT03047980)

Last Updated: 2021-11-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

10 participants

Primary outcome timeframe

Baseline and at 6 months on the study drug

Results posted on

2021-11-01

Participant Flow

All enrolled participants will receive oral sirolimus.

Participant milestones

Participant milestones
Measure	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. Sirolimus: Low dose oral sirolimus
Overall Study STARTED	10
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Sirolimus: Low dose oral sirolimus
Overall Study Adverse Event	1

Baseline Characteristics

Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sirolimus n=10 Participants 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. Sirolimus: Low dose oral sirolimus
Age, Categorical <=18 years	9 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants
Age, Continuous	12.58 years STANDARD_DEVIATION 5.17 • n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	5 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	9 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	10 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline and at 6 months on the study drug

Outcome measures

Outcome measures
Measure	Sirolimus n=9 Participants 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. Sirolimus: Low dose oral sirolimus
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Vocabulary Baseline	44.2 T score Standard Deviation 12.5
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Vocabulary Follow-up	42.3 T score Standard Deviation 12.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Attention Baseline	34.1 T score Standard Deviation 10.5
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Attention Follow-up	35.2 T score Standard Deviation 14.1
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Working Memory Baseline	26.3 T score Standard Deviation 9.8
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Working Memory Follow-up	28.1 T score Standard Deviation 3.9
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Executive Function Baseline	33.1 T score Standard Deviation 10.2
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Executive Function Follow-up	35.7 T score Standard Deviation 15.4
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Processing Speed Baseline	27.0 T score Standard Deviation 14.5
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Processing Speed Follow-up	36.4 T score Standard Deviation 17.6
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Sequential Memory Baseline	39.3 T score Standard Deviation 12.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Sequential Memory Follow-up	40.9 T score Standard Deviation 8.6
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Recognition Baseline	37.7 T score Standard Deviation 12.8
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery National Institute of Health Toolbox Recognition Follow-up	36.0 T score Standard Deviation 10.4
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Baseline	43.5 T score Standard Deviation 8.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Follow-up	35.4 T score Standard Deviation 20.5
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Baseline	45.9 T score Standard Deviation 7.9
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Follow-up	35.7 T score Standard Deviation 20.4
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Baseline	53.8 T score Standard Deviation 5.1
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Follow-up	36.7 T score Standard Deviation 15.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference	49.2 T score Standard Deviation 11.1
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System Pain (PROMIS) Interference Follow-up	36.1 T score Standard Deviation 18.8
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Baseline	46.9 T score Standard Deviation 10.9
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Interference Follow-up	41.9 T score Standard Deviation 15.7
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Peer Relations Baseline	49.8 T score Standard Deviation 10.9
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Patient-Reported Outcomes Measurement Information System (PROMIS) Peer Relations Follow-up	44.1 T score Standard Deviation 17.5
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Grip Strength Dominant Baseline	39.0 T score Standard Deviation 14.4
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Grip Strength Dominant Follow-up	42.0 T score Standard Deviation 5.1
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Grip Strength Non-Dominant Baseline	26.1 T score Standard Deviation 28.2
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Grip Strength Non-Dominant Follow-up	20.6 T score Standard Deviation 28.9
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Dexterity Dominant Baseline	30.6 T score Standard Deviation 16.8
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Dexterity Dominant Follow-up	31.6 T score Standard Deviation 14.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Dexterity Non-Dominant Baseline	31.6 T score Standard Deviation 14.3
Change in Cognitive Function as Assessed by the National Institute of Health (NIH) Toolbox Cognitive Battery Dexterity Non-Dominant Follow-up	30.1 T score Standard Deviation 19.9

SECONDARY outcome

Timeframe: Baseline and at 6months on the study drug

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).

Outcome measures

Outcome measures
Measure	Sirolimus n=10 Participants 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. Sirolimus: Low dose oral sirolimus
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band Patients with Stroke-Like Episodes Baseline	0.686 score on a scale Standard Deviation 0.03
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band Patients with Stroke-Like Episodes Follow-up	0.426 score on a scale Standard Deviation 0.19
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band Patients without Stroke-like episodes Baseline	0.167 score on a scale Standard Deviation 0.23
Difference in Mean Power Asymmetry of the Occipital Alpha Frequency Band Patients without stroke-line episodes follow-up	0.247 score on a scale Standard Deviation 0.13

SECONDARY outcome

Timeframe: Baseline and at 6 months on the study drug

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.

Outcome measures

Outcome measures
Measure	Sirolimus n=10 Participants 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. Sirolimus: Low dose oral sirolimus
Change in Sturge-Weber Syndrome Clinical Neuroscore Composite Score Baseline	4.5 score on a scale Interval 0.0 to 15.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Composite Score Follow-up	4.5 score on a scale Interval 0.0 to 15.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Seizure Score Baseline	1 score on a scale Interval 0.0 to 4.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Seizure Score Follow-Up	1 score on a scale Interval 0.0 to 4.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Hemiparesis Score Baseline	1 score on a scale Interval 0.0 to 4.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Hemiparesis Score Follow-up	1 score on a scale Interval 0.0 to 4.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Visual Field Cut Score Baseline	0.5 score on a scale Interval 0.0 to 2.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Visual Field Cut Score Follow-up	0 score on a scale Interval 0.0 to 2.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Cognitive Function Score Baseline	2.5 score on a scale Interval 0.0 to 5.0
Change in Sturge-Weber Syndrome Clinical Neuroscore Cognitive Function Score Follow-Up	2.5 score on a scale Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sirolimus n=10 Participants 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. Sirolimus: Low dose oral sirolimus
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score Improved Port-Wine Score	4 Participants
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score No Change Port-Wine Score	2 Participants
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score Worsened Port-Wine Score	2 Participants
Number of Participants With a Change in Sturge-Weber Syndrome Birthmark Score No Port-Wine Birthmark	2 Participants

Adverse Events

Sirolimus

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sirolimus n=10 participants at risk 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. Sirolimus: Low dose oral sirolimus
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.

Other adverse events

Other adverse events
Measure	Sirolimus n=10 participants at risk 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. Sirolimus: Low dose oral sirolimus
Gastrointestinal disorders Abdominal Pain	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Skin and subcutaneous tissue disorders Skin Ulceration in Mouth	30.0% 3/10 • Number of events 7 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Gastrointestinal disorders Nausea	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Infections and infestations Upper Respiratory Infection	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Investigations Increased Alanine Aminotransferase	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Investigations Increased aspartate aminotransferase	20.0% 2/10 • Number of events 3 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Investigations Cholesterol High	10.0% 1/10 • Number of events 4 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Metabolism and nutrition disorders Hypertriglyceridemia	40.0% 4/10 • Number of events 9 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Investigations Decreased HDL Cholesterol	20.0% 2/10 • Number of events 9 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Renal and urinary disorders Abnormal Urine Labs	10.0% 1/10 • Number of events 2 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Nervous system disorders Headache	20.0% 2/10 • Number of events 4 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Nervous system disorders Seizure	10.0% 1/10 • Number of events 2 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Nervous system disorders Somnolence	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Product Issues Personality Change	20.0% 2/10 • Number of events 2 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.
Psychiatric disorders Behavioral Issues/ Aggression	10.0% 1/10 • Number of events 1 • 6 months The Rare Diseases Clinical Research Network defines an adverse event as "...an unfavorable and unintended sign, symptom or disease associated with a participants' participation in a Rare Disease Clinical Research Network Study." The three types of adverse events are serious adverse events, unexpected adverse events and expected adverse events. This classification is using Common Terminology Criteria for Adverse Events developed and maintained by CTEP at National Cancer Institute.

Additional Information

Research Assistant

Kennedy Krieger Institute

Phone: 443-923-9569

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place