Study to Assess the Effect of Cannabidiol on Liver Fat Levels in Subjects With Fatty Liver Disease.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01284634
First received: January 26, 2011
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to assess the effect of cannabidiol (CBD) on liver triglyceride (liver fat) in subjects with fatty liver disease.


Condition Intervention Phase
Fatty Liver
Drug: Cannabidiol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Partially-blind, Placebo-controlled, Pilot, Dose-ranging Study to Assess the Effect of Cannabidiol on Liver Fat Levels in Subjects With Fatty Liver Disease

Resource links provided by NLM:


Further study details as provided by GW Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • Change From Baseline to the End of Treatment in Mean % Liver Triglyceride Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Liver triglyceride levels (%) were measured by MRI/MRS scanning and the change from baseline to end of treatment in group mean levels were investigated. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.


Secondary Outcome Measures:
  • Change From Baseline to the End of Treatment it Mean Serum Total Cholesterol Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was taken for the measurement of serum total cholesterol. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Serum High Density Lipoprotein (HDL)-Cholesterol(C) Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of HDL-C. An increase from baseline (i.e. a positive value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Serum Low Density Lipoprotein (LDL)-Cholesterol(C) Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of LDL-C. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment it the Mean Serum HDL:LDL Cholesterol Ratio [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of HDL-C and LDL-C, allowing the HDL:LDL cholesterol ratio to be calculated. An increase from baseline (i.e. a positive value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Serum Triglyceride Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of serum triglycerides. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Fasting Plasma Glucose Levels [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of fasting plasma glucose. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Body Mass Index (BMI) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Individual subject's BMIs were calculated by dividing mass (kg) by height (m2). A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Body Weight [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Body weight (kg) was measured at baseline and the end of treatment. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Waist-to-hip Ratio [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    The waist-to-hip ratio was calculated at baseline and the end of treatment. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Neck Measurement [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    The neck circumference was measured at baseline and the end of treatment. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Waist Measurement [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Waist circumference was measured at baseline and the end of treatment. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Hip Measurement [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Hip circumference was measured at baseline and the end of treatment. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Chest/Pectoral) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Midaxillary) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Triceps) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Subscapular) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Abdomen) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Suprailiac) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Skin-fold Thickness (Thigh) [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Skin fold thickness measurements were the mean of three measurements per site calculated for each subject. If one or more measurements were missing for a site, then the mean was calculated over the available measurement(s) for that site. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Skin-fold Thickness [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Total skin fold thickness was based on the sum of the average values from the seven sites stated above. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Visceral Abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Subcutaneous Abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Internal Non-abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Subcutaneous Non-abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Non-abdominal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Internal Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Subcutaneous Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    As measured by MRI/MRS scanning. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Fat [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Total fat = total abdominal + total non-abdominal fat. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Abdominal Adiposity [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    Abdominal adiposity = ratio of total abdominal to total non-abdominal fat. A reduction from baseline (i.e. a negative value) indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Total Fat as a Percentage of Body Weight [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A reduction from baseline (i.e. a negative value) in the amount of fat as a percentage of body weight indicates an improvement in condition.

  • Change From Baseline to the End of Treatment in Mean Fasting Serum Insulin [ Time Frame: After 56 days of treatment ] [ Designated as safety issue: No ]
    A fasting blood sample was obtained for the measurement of fasting serum insulin. An increase from baseline (i.e. a positive value) indicates an improvement in condition.

  • Incidence of Adverse Events (AEs) as a Measure of Patient Safety [ Time Frame: From 0 -10 weeks (study duration) ] [ Designated as safety issue: Yes ]
    All reported AEs were classified by system organ class (SOC), preferred term (PT) and low level term using version 13.1 of the MedDRA dictionary. The number of subjects who experienced an AE during the study is presented.


Enrollment: 25
Study Start Date: February 2011
Study Completion Date: September 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low dose cannabidiol/placebo Drug: Cannabidiol
1 x 100 mg CBD/placebo twice daily (200 mg daily)
Active Comparator: Mid dose cannabidiol/placebo Drug: Cannabidiol
2 x 100 mg CBD/placebo twice daily (400 mg)
Active Comparator: High dose cannabidiol/placebo Drug: Cannabidiol
4 x 100 mg CBD/placebo twice daily (800 mg daily)

  Hide Detailed Description

Detailed Description:

This 10 week (2-10 day screening, eight week treatment period and one week follow-up), randomized, partially-blind study will assess the effect of CBD in subjects with raised liver triglycerides (liver fat ≥ 5%).

Eligible subjects will enter the study at a Screening Visit (Visit 1, Day -10 to -2) and commence a two to ten day screening period, before returning for a baseline visit (Visit 2, Day 1).

During the fasted Screening Visit, study-related observations will include: informed consent, demographics, medical history, physical examination, electrocardiogram (ECG), vital signs, weight, height and concomitant medications.

Subjects will have the following assessments performed:

  1. Fasting lipid profile blood sample
  2. Fasting plasma glucose, HbA1c & fasting serum insulin
  3. Safety blood tests (haematology and biochemistry)
  4. Urinalysis (including drugs of abuse screen)
  5. CAGE Questionnaire to assess alcohol dependency
  6. Body weight will be measured and BMI calculated
  7. Pregnancy test (if appropriate)
  8. Liver triglyceride content (Magnetic Resonance Spectroscopy (MRS)) scan unless there is documented history of a liver fat content equal to or above 5% as measured by Magnetic Resonance Imaging (MRI)/MRS or a biopsy within the last two months prior to this screening visit. Where subjects (and/or carers) feel the scan poses a significant burden (in addition to the other visit procedures), the fasted scan may be undertaken separately with the remaining visit procedures completed within 72 hours of the visit. Suitable subjects will be invited to return fasted for a Baseline Visit (Visit 2, Day 1). The following measurements will be made at Visit 2, prior to study medication being dispensed:

1) Safety assessments (Adverse Event(s) (AE)) and vital signs and a review of concomitant medications) 2) Body weight measurements / adipose tissue distribution. Body fat content and visceral adiposity will be assessed by MRI/MRS. Where subjects (and/or carers) feel the scan poses a significant burden (in addition to the other visit procedures), the fasted scan may be undertaken separately with the remaining visit procedures completed within 72 hours of the visit. 3) Fasting lipid blood sample 4) Fasting plasma glucose and serum insulin 5) Safety blood sample (haematology and biochemistry) 6) Urinalysis 7) Liver triglyceride content (MRI/MRS scan). Where subjects (and/or carers) feel the scan poses a significant burden (in addition to the other visit procedures), the fasted scan may be undertaken separately with the remaining visit procedures completed within 72 hours of the visit.

8) Other assessments (blood sample for plasma CBD levels; Physical Activity Questionnaire; Food Frequency Questionnaire) Subjects will be issued study medication and advised to take it twice daily as instructed.

There will be a safety follow-up telephone call at Week 1, Day 8 (Visit 3) which will involve a review of any new or ongoing AEs and changes to concomitant medications. Compliance with IMP administration will also be discussed.

There will be a second safety follow-up telephone call at Week 2, Day 15 (Visit 4), which will involve a review of any new or ongoing AEs and changes to concomitant medications. Compliance with IMP administration will also be discussed.

A further visit will take place mid-treatment (Visit 5, Week 4, Day 29) where the following assessments will be performed:

  1. Safety assessments (AEs, vital signs, review of concomitant medications and physical exam)
  2. Safety blood sample (haematology, biochemistry and non-fasting glucose)
  3. Urinalysis
  4. IMP compliance review There will be a safety follow-up telephone call at Week 6, Day 43 (Visit 6) which will involve a review of any new or ongoing AEs and changes to concomitant medications. Compliance with IMP administration will also be discussed.

A further fasted visit will take place at the end of treatment (Visit 7, Day 57) where the following assessments will be performed:

  1. Safety assessments (AEs, vital signs, review of concomitant medications, physical exam (including body weight measurements and BMI calculation), ECG and pregnancy test as appropriate)
  2. Body weight measurements / adipose tissue distribution
  3. Fasting lipid blood sample
  4. Fasting plasma glucose and serum insulin
  5. Safety blood sample (haematology and biochemistry)
  6. Urinalysis (including drugs of abuse screen)
  7. Liver triglyceride content (MRI/MRS scan). Where subjects (and/or carers) feel the scan poses a significant burden (in addition to the other visit procedures), the fasted scan may be undertaken separately with the remaining visit procedures completed within 72 hours of the visit.
  8. Other assessments (blood sample for plasma CBD levels; Physical Activity Questionnaire; Food Frequency Questionnaire)
  9. IMP compliance review There will be a final safety follow-up telephone call at Visit 8 (seven days after completion or withdrawal), involving a review of any new or ongoing AEs and changes to concomitant medications.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is willing and able to give informed consent for participation in the study.
  • Subject is aged 18 years or above.
  • Subjects with documented evidence of liver fat content equal to or above 5% as measured by MRI/MRS or a biopsy within two months, or willing to undergo MRI/MRS scan at Visit 1 to confirm a liver fat content of equal to or above 5%.
  • In the opinion of the investigator, no changes in levels of exercise for four weeks and diet (as assessed by the physical activity questionnaire and food frequency questionnaire) prior to the start of treatment and subject agrees to keep stable for the duration of the study.
  • Subject is able (in the investigator's opinion), and willing to comply with all study requirements.
  • Subject is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable.
  • Subject is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

  • Clinical diagnosis or treatment for Type I/II diabetes.
  • Subject has received an unapproved IMP within the 30 days prior to the screening visit.
  • Currently receiving a prohibited medication and unwilling to stop for 14 days prior to the screening visit and for the duration of the study.
  • Currently using or has used recreational cannabis, medicinal cannabis or cannabinoid medications (including Sativex)within one month prior to study entry and unwilling to abstain for the duration of the study.
  • Any known or suspected history of: alcohol or substance abuse epilepsy or recurrent seizures.
  • Any know or suspected history of major depression sufficient to require treatment or disrupt ordinary life (excluding episodes of reactive depression - in the opinion of the investigator).
  • Clinically significant cardiac, renal or hepatic impairment in the opinion of the investigator.
  • Known history of Hepatitis B or C.
  • Genetic dyslipidaemia in the opinion of the investigator.
  • Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, may influence the result of the study, or the subject's ability to participate in the study.
  • Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s).
  • Presence of any metal implants.
  • Any known or suspected history of claustrophobia.
  • Female subjects of child bearing potential not able or willing to use effective contraception for the duration of the study and for three months thereafter or male subjects whose partner is of child bearing potential, who are not willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
  • Female subject who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
  • Weighing >150 kg.
  • Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator would prevent the subject from safe participation in the study.
  • Unwilling to abstain from donation of blood during the study.
  • Travel outside the country of residence planned during the study.
  • Subject has previously enrolled into this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01284634

Locations
United Kingdom
Imperial College Healthcare NHS Trust, Robert Steiner MRI Unit, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Road
London, United Kingdom, W120NN
MAC UK
Manchester, United Kingdom, M32 0UT
Manchester Royal Infirmary
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
GW Pharmaceuticals Ltd.
Investigators
Principal Investigator: Anthony P Goldstone, BM BCh,MRCP,PhD Imperial College Healthcare NHS Trust
  More Information

No publications provided

Responsible Party: GW Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01284634     History of Changes
Other Study ID Numbers: GWMD09112, 2009-017080-41
Study First Received: January 26, 2011
Results First Received: December 3, 2013
Last Updated: December 3, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GW Pharmaceuticals Ltd.:
Cannabidiol
Fatty liver
Diabetes
Body fat

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 15, 2014