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| ID | Type | Description | Link |
|---|---|---|---|
| U01DA033267 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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Cannabis dependence is associated with changes in the brain's cannabinoid system. When cannabis dependent individuals try to quit using cannabis, some of them experience problems that make it difficult for them to achieve and maintain abstinence. Therefore, reducing the problems related to quitting cannabis may facilitate abstinence. One way to do this is by harnessing the brain's capacity to make its own cannabis-like substances - endocannabinoids. One of the main endocannabinoids is anandamide. The study is based on the hypothesis that the problems related to quitting cannabis use will be reduced by increasing the brain levels of anandamide. Furthermore, by reducing the problems related to quitting cannabis, people will be less likely to relapse. Brain anandamide levels will be increased by blocking the breakdown of anandamide using a fatty acid amide hydrolase inhibitor (FAAH-I). The effects of a novel FAAH-I cannabis withdrawal and relapse in cannabis dependent subjects will be studied in a double-blind, randomized, controlled, proof-of-concept study. Cannabis-dependent subjects will receive placebo or the FAAH-inhibitor PF-04457845 in a 2:1 randomization. The trial consists of a 1 week inpatient stay to achieve abstinence, a 3 week outpatient treatment phase. Cannabis withdrawal will be measured during the inpatient phase. Cannabis use and urinary THC-COOH levels will be measured during the entire study. The treatment phase will be followed by a safety follow up phase of 8 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-04457845 | Active Comparator | 2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg |
|
| Placebo (sugar pill) | Placebo Comparator | 1/3 of subjects will be randomized to placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-04457845 | Drug | Study medication will be administered at 4mg by mouth daily for four weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Marijuana Withdrawal Checklist (MWC) | 32-item checklist evaluating potential symptoms of cannabis withdrawal, lower values reflect lesser severity of withdrawal symptoms (lower scores represent a better outcome). Min: 0 Max: 96 | The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. |
| Change in Self Reported Cannabis Use at the End of 4 Weeks | Subject quantifies and reports frequency of cannabis use prior to study participation and during the 4 week period. Lower scores reflect less cannabis usage, while higher scores reflect more frequent usage. Min: 0 Max: undeterminable, varies per patient and their usage. | Administered weekly for 4 weeks to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. |
| Change in THC-COOH Quantification at the End of 4 Weeks | Subjects provide urine samples to quantify levels of THC. | Samples obtained weekly for 4 weeks to assess change from baseline (Day 0). The results from each time point and subject were calculated to report the mean score for each arm. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Polysomnography | Polysomnography (PSG) is a comprehensive reading of biophysiological changes that occur during sleep, including identification of sleep stage. A mean and standard deviation of their data points during sleep stages were calculated to determine change from baseline to the end of study treatment. | Polysomnography was collected two nights prior to baseline visit, for three nights during study treatment and two nights after four weeks of study treatment. A mean was calculated to assess change from baseline (Day 0). |
| Measure | Description | Time Frame |
|---|---|---|
| Feeling States | Visual analog scale for feeling states (depression, anxiety, irritability) | Administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (Once pre-treatment and during the inpatient phase 'acute abstinence') to assess change from baseline (Day 0) |
| Plasma Endocannabinoid Levels |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Deepak C D'Souza, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06511 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30528676 | Derived | D'Souza DC, Cortes-Briones J, Creatura G, Bluez G, Thurnauer H, Deaso E, Bielen K, Surti T, Radhakrishnan R, Gupta A, Gupta S, Cahill J, Sherif MA, Makriyannis A, Morgan PT, Ranganathan M, Skosnik PD. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. Lancet Psychiatry. 2019 Jan;6(1):35-45. doi: 10.1016/S2215-0366(18)30427-9. Epub 2018 Dec 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | PF-04457845 (4mg by Mouth Daily for 4 Weeks) | 2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg PF-04457845: Study medication will be administered at 4mg by mouth daily for four weeks. |
| FG001 | Placebo (Sugar Pill, by Mouth Daily for 4 Weeks) | 1/3 of subjects will be randomized to placebo Placebo: Sugar pill |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PF-04457845 (4mg by Mouth Daily for 4 Weeks) | 2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg PF-04457845: Study medication will be administered at 4mg by mouth daily for four weeks. |
| BG001 | Placebo (Sugar Pill, by Mouth Daily for 4 Weeks) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Marijuana Withdrawal Checklist (MWC) | 32-item checklist evaluating potential symptoms of cannabis withdrawal, lower values reflect lesser severity of withdrawal symptoms (lower scores represent a better outcome). Min: 0 Max: 96 | Missing data and the removal of outliers led to differences between the total number of participants and the sample for this variable | Posted | Mean | 95% Confidence Interval | score on a scale | The MWC was administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (during the inpatient phase when withdrawal peaks) to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-04457845 (4mg by Mouth Daily for 4 Weeks) | 2/3 of subjects will be randomized to fatty acid amide hydrolase (FAAH) inhibitor 4mg PF-04457845: Study medication will be administered at 4mg by mouth daily for four weeks. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Deepak Cyril D'Souza, MD | Yale University School of Medicine | 203-932-5711 | 2594 | deepak.dsouza@yale.edu |
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| ID | Term |
|---|---|
| D002189 | Marijuana Abuse |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C560620 | N-pyridazin-3-yl-4-(3-((5-(trifluoromethyl)pyridin-2-yl)oxy)benzylidene)piperidine-1-carboxamide |
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| Placebo | Drug | Sugar pill |
|
Measurement of circulating plasma Anandamide |
| Samples obtained at the following study visits: Day -1, Day 0, Day 2, Day 4, Week 2, Week 3, Week 4 to assess change from baseline (Day 0) |
1/3 of subjects will be randomized to placebo Placebo: Sugar pill |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Placebo (Sugar Pill, by Mouth Daily for 4 Weeks) | 1/3 of subjects will be randomized to placebo Placebo: Sugar pill |
|
|
| Primary | Change in Self Reported Cannabis Use at the End of 4 Weeks | Subject quantifies and reports frequency of cannabis use prior to study participation and during the 4 week period. Lower scores reflect less cannabis usage, while higher scores reflect more frequent usage. Min: 0 Max: undeterminable, varies per patient and their usage. | Missing data and the removal of outliers led to differences between the total number of participants and the sample for this variable | Posted | Mean | 95% Confidence Interval | joints per day | Administered weekly for 4 weeks to assess change from baseline (Day 0). The scores from each time point and subject were calculated to report the mean score for each arm. |
|
|
|
| Primary | Change in THC-COOH Quantification at the End of 4 Weeks | Subjects provide urine samples to quantify levels of THC. | Missing data and the removal of outliers led to differences between the total number of participants and the sample for this variable | Posted | Mean | 95% Confidence Interval | ng/mL | Samples obtained weekly for 4 weeks to assess change from baseline (Day 0). The results from each time point and subject were calculated to report the mean score for each arm. |
|
|
|
| Secondary | Change in Polysomnography | Polysomnography (PSG) is a comprehensive reading of biophysiological changes that occur during sleep, including identification of sleep stage. A mean and standard deviation of their data points during sleep stages were calculated to determine change from baseline to the end of study treatment. | The units analyzed reflects the number of data points (sum of participants per drug condition across time) was 42 in the placebo group and 82 in the PF-04457845 group. Missing data and the removal of outliers led to differences between the total number of participants and the sample for this variable. | Posted | Mean | Standard Deviation | minutes | Polysomnography was collected two nights prior to baseline visit, for three nights during study treatment and two nights after four weeks of study treatment. A mean was calculated to assess change from baseline (Day 0). | Number of Data Points | Number of Data Points |
|
|
|
| Other Pre-specified | Feeling States | Visual analog scale for feeling states (depression, anxiety, irritability) | Not Posted | Administered on Day 0, Day 1, Day 2, Day 3, and Day 4 (Once pre-treatment and during the inpatient phase 'acute abstinence') to assess change from baseline (Day 0) | Participants |
| Other Pre-specified | Plasma Endocannabinoid Levels | Measurement of circulating plasma Anandamide | Not Posted | Samples obtained at the following study visits: Day -1, Day 0, Day 2, Day 4, Week 2, Week 3, Week 4 to assess change from baseline (Day 0) | Participants |
| 0 |
| 46 |
| 0 |
| 46 |
| 31 |
| 46 |
| EG001 | Placebo (Sugar Pill, by Mouth Daily for 4 Weeks) | 1/3 of subjects will be randomized to placebo Placebo: Sugar pill | 0 | 24 | 0 | 24 | 14 | 24 |
| Trouble Concentrating | Nervous system disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Stuffy Nose | General disorders | Systematic Assessment |
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| Sneezing | General disorders | Systematic Assessment |
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| Fluid Filled Cyst on Left Wrist | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Chest Congestion | General disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Red Marks/Skin Irritation at PSG Electrode Placement | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash from Tape used for PSG Electrode Application | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Eye Twitch | Eye disorders | Systematic Assessment |
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| Lightheaded after Blood Draw | Nervous system disorders | Systematic Assessment |
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| Right Shoulder Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Loose Stool | Gastrointestinal disorders | Systematic Assessment |
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| Gastric Paralysis | Gastrointestinal disorders | Systematic Assessment |
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| Chronic Gastritis | Gastrointestinal disorders | Systematic Assessment |
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| High Blood Pressure | Cardiac disorders | Systematic Assessment |
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| Increased Appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Syncopal Episode (Related to Phlebotomy) | Nervous system disorders | Systematic Assessment |
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| Sleep Disturbances | Nervous system disorders | Systematic Assessment |
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| Itchy Throat | General disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Jammed Pinky Finger | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Feet Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Upper Respiratory Infection | Infections and infestations | Systematic Assessment |
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| Scratched Cornea | Eye disorders | Systematic Assessment |
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| Lower Back Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Sharp Rib Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Pressure in Head | Nervous system disorders | Systematic Assessment |
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| Sinus Pressure | General disorders | Systematic Assessment |
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| Tooth Pain | General disorders | Systematic Assessment |
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| Muscle Strain in Back | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Runny Nose | General disorders | Systematic Assessment |
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| Itchy Throat | General disorders | Systematic Assessment |
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| Sore Throat | General disorders | Systematic Assessment |
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| Dry Skin on Face | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Foot Laceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Cyst Under Eye | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Swollen Lymph Node in Groin | Blood and lymphatic system disorders | Systematic Assessment |
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| Lyme Disease | Nervous system disorders | Systematic Assessment |
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| Chest Tightness | General disorders | Systematic Assessment |
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| Feeling Faint | General disorders | Systematic Assessment |
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| Trouble Sleeping | Nervous system disorders | Systematic Assessment |
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| Concussion | Nervous system disorders | Systematic Assessment |
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| Ringworm | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Low Phosphorus Levels | Vascular disorders | Systematic Assessment |
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| Ear Popping | Ear and labyrinth disorders | Systematic Assessment |
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| Worsening of Existing Hernia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Nose Bleed | General disorders | Systematic Assessment |
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| Gas | Gastrointestinal disorders | Systematic Assessment |
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| Burst Blood Vessel in Right Eye | Eye disorders | Systematic Assessment |
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| Knee Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Sweating | General disorders | Systematic Assessment |
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