Clinical trial NCT03848481: CBDV vs Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)
Official title: Cannabidivarin (CBDV) vs. Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prader-Willi Syndrome
Keywords: PWS
Prader- Willi Syndrome
Irritability
CBDV
Cannabinoids
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Foundation for Prader-Willi Research
name: GW Pharmaceuticals Ltd
First posted: 2019-02-20
Enrollment: 14
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to examine the feasibility and safety of cannabidivarin (CBDV) as a treatment for children and young adults with PWS.

Detailed description: This clinical research trial aims to study the feasibility and safety of cannabidivarin (CBDV), in children and young adults with Prader-Willi Syndrome (PWS). CBDV has effects independent of CB1 and CB2 receptor activation and a good safety profile. This proposal addresses the Foundation for Prader Willi Research's PWS Research Plan: Program 1, Clinical Care Research: seeks to evaluate treatments that aim to reduce behavioral symptoms, such as irritability, in order to improve the quality of life of both the individual with PWS and their families. GW Pharmaceuticals will provide the CBDV drug and matching placebo.

Eligibility criteria: Inclusion Criteria

1. Male or Female outpatients aged 5 to 30 years.
2. Diagnosis of PWS confirmed by genetic testing and patient medical records and history.
3. Stable pharmacologic, educational, behavioral and/or dietary interventions for 4 weeks prior to the study start, and for the duration of the study.
4. Have a physical exam and laboratory results that are within the norms for PWS
5. Presence of a parent/caregiver/guardian that is able to consent for their participation and complete assessments regarding the patient's development and behavior throughout the study. Child Assent will be obtained if the subject is 7 years of age or older and has the mental capacity to understand and sign a written assent form and/or give verbal assent.
6. Score on the Clinical Global Impression Scale Severity (CGI-S) ≥ 4 (moderate severity) at baseline.
7. Score of ≥18 on the Aberrant Behavior Checklist-Irritability (ABC-I) at baseline.
8. Agree not to drive or operate machinery.

Exclusion Criteria

1. Exposure to any investigational agent in the 30 days prior to randomization.
2. Prior chronic treatment with CBD or CBDV.
3. Positive testing for THC or other drugs of abuse via urine testing at the screening visit or baseline visits upon repeat confirmation testing.
4. History of Drug Abuse Disorder including Cannabis Use Disorder
5. A primary psychiatric diagnosis other than PWS, including bipolar disorder, psychosis, schizophrenia, PTSD or MDD. These patients will be excluded due to potential confounding results.
6. A medical condition that severely impacts the subject's ability to participate in the study, interferes with the conduct of the study, confounds interpretation of study results or endangers the subject's well-being (including but not limited to hepatic or renal impairment and cardiovascular disease).
7. Known or suspected allergy to CBDV or excipients used in the formulation (i.e. sesame).
8. Clinical indications of renal, pancreatic, or hematologic dysfunction as evidenced by values above upper limits of normal for BUN/creatinine, values twice the upper limit of normal for serum lipase and amylase, platelets \<80,000 /mcL, WBC\<3.0 103 /mcL. or \> 2 X UNL values of AST or ALT.
9. ECG abnormality at baseline screening or clinically significant postural drop in systolic blood pressure at screening. If the initial screening ECG shows a QTcB of greater than 460 msec, then 2 additional ECGs will be conducted in the same sitting, 5 minutes apart. If not recognized at screening, then a full triplicate repeat showing an average QTcB of 460 msec or less to meet all inclusion/exclusion criteria
10. Female subjects who are pregnant will be excluded from the study. If a female subject is able to become pregnant, she will be given a pregnancy test before entry into the study. Female subjects will be informed not become pregnant while taking CBDV. Female subjects must tell the investigator and consult an obstetrician or maternal-fetal specialist if they become pregnant during the study.

Primary outcomes:
measure: Aberrant Behavior Checklist-Irritability Subscale (ABC-I)
timeFrame: from Baseline to Week 12
Secondary outcomes:
measure: Repetative Behavior Scale- Revised (RBS-R)
timeFrame: from Baseline to Week 12
measure: Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
timeFrame: from Baseline to Week 12
measure: Hyperphagia Questionnaire for Clinical Trials (HQ-CT)
timeFrame: from Baseline to Week 12
measure: ActiGraph GT9X-BT activity monitors
timeFrame: from Baseline to Week 12
measure: Clinical Global Impression Scale - Improvement (CGI-I)
timeFrame: from Baseline to Week 12
measure: Caregiver Strain Questionnaire (CSQ)
timeFrame: from Baseline to Week 12
measure: Montefiore Einstein Rigidity Scale-Revised-PWS (MERS-R-PWS)
timeFrame: from Baseline to Week 12
measure: Aberrant Behavior Checklist (ABC) subscales in lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech
timeFrame: from Baseline to Week 12
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center, Albert Einstein College of Medicine
state: New York
Study officials:
affiliation: Montefiore Medical Center/Albert Einstein College of Medicine
name: Eric Hollander, MD
role: PRINCIPAL_INVESTIGATOR
References: