CBDV vs Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)

Cannabidivarin (CBDV) vs. Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)

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

Study Overview

• Status: Terminated
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: CBDV Compound

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 Cannabinoid Receptor Type 1 (CB1) and Cannabinoid Receptor Type 2 (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 (since acquired by Jazz Pharmaceuticals) will provide the CBDV drug and matching placebo.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center, Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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, Post-Traumatic Stress Disorder (PTSD), or Major Depressive Disorder (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 Blood Urea Nitrogen (BUN)/creatinine, values twice the upper limit of normal for serum lipase and amylase, platelets <80,000 /microliter, white blood cell (WBC)<3.0 103 /microliter or > 2x Upper Limit of Normal (UNL) values of aspartate aminotransferase (AST) or alanine aminotransferase (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 Bazett's corrected QT interval (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabidivarin (CBDV); Weight-based dosing of 10 mg/kg/day of CBDV for 12 weeks	Drug: CBDV Compound; CBDV is obtained from the Cannabis sativa L. plant and contains a negligible quantity (less than 0.2%) of Tetrahydrocannabinol (THC).
Placebo Comparator: Matched Placebo; Weight-based dosing of 10 mg/kg/day of placebo for 12 weeks	Drug: Placebo; Placebo oral solution contains matching excipients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritability Based on Aberrant Behavior Checklist-Irritability (ABC-I) Subscale	Irritability will be assessed using the Aberrant Behavior Checklist-Irritability Subscale (ABC-I). The ABC-I is a well-characterized outcome that is accepted by the FDA for the purpose of labeling and is one of the best and most validated outcome measures in the developmental disabilities. The ABC-Irritability subscale consists of 15 questions that address the presence of irritability, aggression, tantrums and/or self-injury. Each item is rated on a scale ranging from 0 ("Not at all a problem") to 3 ("Severe problem"), resulting in a total score range of 0-45, such that higher ABC-I scores are indicative of more severe behavioral problems. Subjects must score an 18 or higher at screening to be included in the study. ABC-I scores for Week 4, Week 8, and Week 12 are summarized in the table by study arm using descriptive statistics. Baseline results for this outcome can be found in the Baseline Characteristics module.	Baseline, Week 4, Week 8, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repetitive Behavior Based on the Repetitive Behavior Scale-Revised (RBS-R).	Repetitive behavior will be evaluated using the RBS-R. RBS-R is a 43-item self-report questionnaire used to measure the breadth or repetitive behaviors in children, adolescents, and adults with ASD. The RBS-R consists of 6 subscales: Stereotyped Behavior, Self-injurious Behavior, Compulsive Behavior, Ritualistic Behavior, Sameness Behavior, and Restricted Behavior that have no overlap of item content. Each of the 43 items are rated on a 4-point Likert scale ranging from 0 ("Behavior does not occur") to 3 ("Behavior occurs and is a severe problem"), yielding an overall scoring range of 0-129, such that higher scores are associated with increased severity of the problem behavior. RBS-R scores for Week 4, Week 8, and Week 12 are summarized in the table by study arm using descriptive statistics. Baseline results for this outcome can be found in the Baseline Characteristics module.	Baseline, Week 4, Week 8, Week 12
Repetitive Behaviors Based on Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)	Obsessive-compulsive symptoms will be assessed using the CY-BOCS. The CY-BOCS is 10-item clinician-rated measure designed to assess the severity of obsessive-compulsive symptoms in children/adolescents over the prior week. It consists of 5 primary sections: Time, Distress, Interference, Resistance, and Control of Symptoms. The 10 items are rated on a scale from 0 ("No symptoms") to 4 ("Extreme symptoms"), for an overall possible range of 0-40, with higher scores indicative of greater severity of symptoms. CY-BOCS scores for Week 4, Week 8, and Week 12 are summarized by study arm using descriptive statistics. Baseline results for this outcome can be found in the Baseline Characteristics module.	Baseline, Week 4, Week 8, Week 12
Hyperphagia	Hyperphagia will be assessed using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). The HQ-CT is a 9-item caregiver-reported measure of the frequency and intensity of food-seeking behaviors in participants with Prader-Willi Syndrome (PWS) over the prior two-week period. The 9 items are graded on a Likert scale ranging from 0 ("No Hyperphagia") to 4 ("Most severe hyperphagia"), yielding an overall possible scoring range of 0-36, with higher scores indicating greater, more severe hyperphagia. HQ-CT scores for Week 4, Week 8, and Week 12 are summarized by study arm using descriptive statistics. Baseline results for this outcome can be found in the Baseline Characteristics module.	Baseline, Week 4, Week 8, Week 12
Global Functioning	Global Functioning will be assessed using the Clinical Global Impression Scale - Improvement (CGI-I). The CGI-I is a global assessment which measures the change in a participant's illness severity, relative to a baseline, considering all symptoms, behaviors, and functional impairment. It consists of a 7-point clinician-rated scale as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. such that higher scores are indicative of worsening global function. CGI-I scores for Week 4, Week 8, and Week 12 are summarized by study arm using basic descriptive statistics.	Week 4, Week 8, Week 12
Caregiver Strain	Caregiver Strain will be evaluated using the Caregiver Strain Questionnaire (CSQ). The CSQ is a 21-item self-report questionnaire, consisting of 3 subscales, developed to assess caregiver strain/stress for families with a child living with an emotional or behavioral disorder. Items 1-11 assess Objective Strain. Items 12, 16-18, and 20-21 assess Subjective Internalized Strain. Items 13-15, and 19 assess Subjective Externalize Strain. All CSQ items are rated from 1 ("Not at all a problem") to 5 ("Very much a problem"). Scores are calculated by averaging items within each subscale to handle missing data and calculating a Global Score by summing the 3 subscale means for a total possible scale range of 3-15. Higher Global Scores are associated with increased Caregiver Strain. Global results scores for Week 4, Week 8, and Week 12 are summarized by study arm using descriptive statistics. Baseline results for this outcome can be found in the Baseline Characteristics module.	Baseline, Week 4, Week 8, Week 12
Rigid Behavior - Based on the Montefiore-Einstein Rigidity Scale-Revised-Prader-Willi Syndrome Scale (MERS-R-PWS)	Rigid behavior will be assessed based using the MERS-R-PWS. The MERS-R-PWS is a clinician-rated scale designed to assess 3 domains of rigid behavior in individuals with PWS: Behavioral Rigidity (e.g., Insistence on sameness, things must be done in his/her way, etc.) Cognitive Rigidity (e.g., Special interests, inflexible adherence to rules, etc.) Protest (in response to deviation from rigidity; e.g., tantrum, irritability, arguing) Each domain consists of 4 items rated on a 5-point scale ranging from 0 ("No/None/Not difficult") to 4 ("Extreme/Extremely Difficult"), yielding a range of 0-16. Scores at Week 12 will only be completed for subjects who display rigid behaviors at baseline, week 4, week 8 and week 12. A total MERS-R-PWS score (0-48) is obtained by summing subscale score. Individual subscale scores (0-16) are also summarized. Higher MERS-R-PWS scores are indicative of greater rigidity within each domain and overall rigidity.	Week 12
Aberrant Behavior	Aberrant Behavior will be assessed using the Aberrant Behavior Checklist (ABC). The ABC is a 58-item informative rating instrument used to measure maladaptive behaviors in individuals with developmental disabilities and ASD which resolves into 5 subscales: Irritability (15 items); Lethargy/Social withdrawal (16 items); Stereotypic behavior (7 items); Hyperactivity/noncompliance (16 items); and Inappropriate speech (4 items). The ABC is completed by a parent/caregiver who knows the participant well. The ABC measures behavior on a 4-point Likert severity scale: (0 = "Not all a problem," 1 = "Slight problem," 2 = "Moderately serious problem," and 3 = "Severe problem"). Scores for 4 of the 5 subscales are reported below (ABC-I results reported as part of the primary outcome). Higher ABC subscale scores indicate greater behavioral severity/dysfunction of that subscale. Week 4, Week 8, and Week 12 scores are summarized by study arm. See Baseline Characteristics module for baseline data.	Baseline, Week 4, Week 8, Week 12
Sleep Quality	Sleep quality will be assessed using ActiGraph GT9X-BT® activity monitors. Successfully screened patients will receive the actigraphy device prior to the onsite baseline visit and will record a minimum of three days of baseline activity data prior to study initiation. The ActiGraph GT9X-BT activity monitors are a well validated activity and sleep monitoring device widely utilized in clinical trials and health research. For this study the ActiGraph monitors will measure: Sleep Latency (the time it takes to fall asleep), Total Sleep Time (the total amount of time spent asleep), and sleep efficiency (percentage of time in bed actually spent sleeping). Sleep data is captured automatically via cloud service. All parameters will be reported in hours/minutes and summarized by study arm.	Baseline through Week 12

Collaborators and Investigators

• Sponsor: Eric Hollander
• Collaborators: Foundation for Prader-Willi Research; GW Pharmaceuticals Ltd
• Investigators: Principal Investigator: Eric Hollander, MD, Montefiore Medical Center/Albert Einstein College of Medicine

Publications and helpful links

General Publications

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• Butler MG, Hossain W, Sulsona C, Driscoll DJ, Manzardo AM. Increased plasma chemokine levels in children with Prader-Willi syndrome. Am J Med Genet A. 2015;167A(3):563-571.
• Viardot A, Sze L, Purtell L, et al. Prader-Willi syndrome is associated with activation of the innate immune system independently of central adiposity and insulin resistance. J Clin Endocrinol Metab. 2010;95(7):3392-3399.
• Irizarry KA, Miller M, Freemark M, Haqq AM. Prader Willi Syndrome: Genetics, Metabolomics, Hormonal Function, and New Approaches to Therapy. Adv Pediatr. 2016;63(1):47-77.
• Rout U, Abdul-Rahman OA, Dhossche DM. An immunological basis of hyperphagia driven by GABAergic dysfunction in Prader-Willi Syndrome. Med Hypotheses. 2012;78(4):462-464.
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• Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55(6):791-802.
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• Jean-Gilles L, Gran B, Constantinescu CS. Interaction between cytokines, cannabinoids and the nervous system. Immunobiology. 2010;215(8):606-610.
• Anavi-Goffer S, Baillie G, Irving AJ, et al. Modulation of L-alpha-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. J Biol Chem. 2012;287(1):91-104.
• Rock EM, Sticht MA, Duncan M, Stott C, Parker LA. Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Delta(9) -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats. Br J Pharmacol. 2013;170(3):671-678.
• Pagano E, Romano B, Iannotti FA, et al. The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients. Pharmacol Res. 2019;149:104464.
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• Deiana S, Watanabe A, Yamasaki Y, et al. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Delta(9)-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour. Psychopharmacology (Berl). 2012;219(3):859-873.
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• McCandless SE, Yanovski JA, Miller J, et al. Effects of MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebocontrolled trial. Diabetes Obes Metab. 2017;19(12):1751-1761.
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Helpful Links

• Research FfP-W. PWS Research Plan 2017-2021. 2017

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CBDV; Irritability; PWS; Cannabinoids; Prader- Willi Syndrome
• Additional Relevant MeSH Terms: Imprinting Disorders; Neurologic Manifestations; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Overnutrition; Neurobehavioral Manifestations; Congenital Abnormalities; Abnormalities, Multiple; Overweight; Intellectual Disability; Obesity; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Prader-Willi Syndrome; cannabidivarin
• Other Study ID Numbers: 2019-9914

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication
• IPD Sharing Time Frame: Following publication for an indefinite period.
• IPD Sharing Access Criteria: Contact Principal Investigator for availability of IPD data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No