Trial Outcomes & Findings for Trial of Cannabis for Essential Tremor (NCT NCT03805750)
NCT ID: NCT03805750
Last Updated: 2022-10-13
Results Overview
The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
7 participants
Primary outcome timeframe
Day 22 (100 minutes post-dose)
Results posted on
2022-10-13
Participant Flow
This is a cross-over design where each subject receives both a placebo and treatment arm in blinded random order.
Participant milestones
| Measure |
CBD/THC First Then Placebo
After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.
|
Placebo First Then CBD/THC
After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.
|
|---|---|---|
|
First Intervention - 4 Weeks
STARTED
|
3
|
4
|
|
First Intervention - 4 Weeks
COMPLETED
|
3
|
4
|
|
First Intervention - 4 Weeks
NOT COMPLETED
|
0
|
0
|
|
Second Intervention - 4 Weeks
STARTED
|
3
|
4
|
|
Second Intervention - 4 Weeks
COMPLETED
|
3
|
2
|
|
Second Intervention - 4 Weeks
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
CBD/THC First Then Placebo
After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.
|
Placebo First Then CBD/THC
After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.
|
|---|---|---|
|
Second Intervention - 4 Weeks
Adverse Event
|
0
|
2
|
Baseline Characteristics
Trial of Cannabis for Essential Tremor
Baseline characteristics by cohort
| Measure |
All Participants
n=7 Participants
After randomization, each patient will receive study medication in two study periods. Each study period includes 1-week titration, 2-week treatment, and 1-week tapering. There is a 3-week washout period between the two study periods. During the titration period, patients will have a starting dose of 1 capsule (placebo or 5mg THC/100mg CBD) per day; 2 capsules per day on day 3; 3 capsules per day on day 6. If the patient or investigator feel that the higher study drug dose of 3 caps per day is causing troublesome side effects, the dosage may be lowered to 2 caps per day. Patients will continue on this target dose during the 2-week treatment and then gradually taper from medication over one week. Patients will crossover to the alternate treatment after a 3-week washout period.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
|
Age, Continuous
|
67.0 years
STANDARD_DEVIATION 11.3 • n=93 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 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
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
7 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
|
7 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 22 (100 minutes post-dose)The tremor mean amplitude calculated using computerized spirography to measure kinetic tremors.
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Digital Spirography
|
1.04 millimeters of tremor amplitude
Standard Deviation 0.57
|
1.00 millimeters of tremor amplitude
Standard Deviation 0.42
|
SECONDARY outcome
Timeframe: Baseline and Day 22The performance sub scale of the TETRAS will be used to measure tremor severity. The scale ranges from 0 to 60 points (0 being no tremor).
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Change in Score on a Scale From Baseline of the Tremor Research Group Essential Tremor Rating Scale (TETRAS)
|
-8.07 score on a scale
Standard Deviation 5.71
|
-10.3 score on a scale
Standard Deviation 3.9
|
SECONDARY outcome
Timeframe: Day 22The Global impression of change will be calculated based on both physician and patient report. The scale ranges from a score of 1 (very much improved) to 7 (very much worse) with a score of 4 indicating 'no change'.
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Global Impression of Change
Clinical Global Impression of Change
|
3 score on a scale
Interval 3.0 to 4.0
|
4 score on a scale
Interval 2.0 to 4.0
|
|
Global Impression of Change
Patient Global Impression of Change
|
3 score on a scale
Interval 3.0 to 4.0
|
4 score on a scale
Interval 2.5 to 4.0
|
SECONDARY outcome
Timeframe: Days 1, 3, 6, 22Side effects survey
Outcome measures
| Measure |
CBD/THC
n=7 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Thumb pain
|
0 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Ringing in ears
|
7 Participants
|
6 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Numbness/tingling
|
4 Participants
|
4 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Dyspnea on exertion
|
4 Participants
|
4 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Watery eyes
|
3 Participants
|
3 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Runny nose
|
3 Participants
|
2 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Decreased concentration
|
7 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Sleepiness
|
4 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Insomnia
|
0 Participants
|
2 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Increased sleepiness
|
2 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Dizziness
|
4 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Memory problems
|
3 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Imbalance
|
3 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Mild headache
|
0 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Groggy
|
0 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Tired
|
0 Participants
|
1 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Anxiety
|
2 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Headache
|
2 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Lightheaded
|
2 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Felt high
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Decreased libido
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Diarrhea
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Dry mouth
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Euphoria
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Fatigue
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Feels relaxed
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Increased thirst
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Felt buzzed
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Quivering voice
|
1 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events Based on Common Terminology Criteria
Visual slowing
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 22This is a scale looking at risk assessment of suicidality. The presence of any positive responses will lead to further evaluation.
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Number of Participants at Risk for Suicide Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 22Electrocardiographic changes from baseline measures will trigger further evaluation. EKG's will be rated as normal/abnormal relative to the baseline EKG reading, and abnormal findings will be rated as clinically significant/not clinically significant.
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Number of Participants With New Study-related Electrocardiogram (EKG) Abnormalities
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and Day 22Population: Participants in both treatment arms will undergone tremor measurement using accelerometry as a surrogate of tremor severity.
The spectral power density measure of accelerometry data to measure will serve as a measure of tremor severity, comparing tremor amplitude from this digital biomarker at the time of the primary outcome to the same measure at baseline.
Outcome measures
| Measure |
CBD/THC
n=5 Participants
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 Participants
Placebo oral capsule: Placebo
|
|---|---|---|
|
Accelerometry-based Assessment of Tremor Severity
|
0.012 Proportion of baseline spectral power
Standard Deviation 0.03
|
0.007 Proportion of baseline spectral power
Standard Deviation 0.011
|
Adverse Events
CBD/THC
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
CBD/THC
n=7 participants at risk
Treatment arm
CBD/THC: Oral formulation of CBD and THC.
|
Placebo
n=7 participants at risk
Placebo oral capsule: Placebo
|
|---|---|---|
|
Ear and labyrinth disorders
Ringing in ears
|
100.0%
7/7 • Over the course of the study period (77 days).
|
85.7%
6/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Numbness/tingling
|
57.1%
4/7 • Over the course of the study period (77 days).
|
57.1%
4/7 • Over the course of the study period (77 days).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea on exertion
|
57.1%
4/7 • Over the course of the study period (77 days).
|
57.1%
4/7 • Over the course of the study period (77 days).
|
|
Eye disorders
Watery eyes
|
42.9%
3/7 • Over the course of the study period (77 days).
|
42.9%
3/7 • Over the course of the study period (77 days).
|
|
Respiratory, thoracic and mediastinal disorders
Runny nose
|
42.9%
3/7 • Over the course of the study period (77 days).
|
28.6%
2/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Decreased concentration
|
100.0%
7/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Sleepiness
|
57.1%
4/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Insomnia
|
0.00%
0/7 • Over the course of the study period (77 days).
|
28.6%
2/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Increased sleepiness
|
28.6%
2/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Dizziness
|
57.1%
4/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Memory problems
|
42.9%
3/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Imbalance
|
42.9%
3/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Mild headache
|
0.00%
0/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Grogginess/cognitive slowing
|
0.00%
0/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Tiredness
|
0.00%
0/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Skin and subcutaneous tissue disorders
Thumb pain
|
0.00%
0/7 • Over the course of the study period (77 days).
|
14.3%
1/7 • Over the course of the study period (77 days).
|
|
Psychiatric disorders
Anxiety
|
28.6%
2/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Headache
|
28.6%
2/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Cardiac disorders
Lightheadedness
|
28.6%
2/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Feeling high/intoxication
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
General disorders
Decreased libido
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Gastrointestinal disorders
Dry mouth
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Psychiatric disorders
Euphoria
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
General disorders
Fatigue
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
General disorders
Feeling relaxed
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Gastrointestinal disorders
Increased thirst
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Nervous system disorders
Felt buzzed
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Respiratory, thoracic and mediastinal disorders
Quivering voice
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
|
Eye disorders
Visual slowing
|
14.3%
1/7 • Over the course of the study period (77 days).
|
0.00%
0/7 • Over the course of the study period (77 days).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place