Trial Outcomes & Findings for Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome (NCT NCT01786109)

NCT ID: NCT01786109

Last Updated: 2013-03-14

Results Overview

Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon. After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 75 participants
• Primary outcome timeframe: 1 hour after drug was ingested
• Results posted on: 2013-03-14

Participant Flow

All participants were recruited from a database of patients with irritable bowel syndrome (IBS) who reside within 120 miles of Rochester, Minnesota

Participant milestones

Measure	Dronabinol 2.5 mg One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg One dose of dronabinol 5 mg will be taken orally with water.	Placebo One dose of placebo will be taken orally with water.
Overall Study STARTED	24	24	27
Overall Study COMPLETED	23	24	25
Overall Study NOT COMPLETED	1	0	2

Reasons for withdrawal

Measure	Dronabinol 2.5 mg One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg One dose of dronabinol 5 mg will be taken orally with water.	Placebo One dose of placebo will be taken orally with water.
Overall Study fail manometry barostat tube placement	1	0	0
Overall Study unrelated illness	0	0	1
Overall Study adverse effects colon preparation	0	0	1

Baseline Characteristics

Effect of a Cannabinoid Agonist on Colonic Sensory Functions in Patients With Irritable Bowel Syndrome

Baseline characteristics by cohort

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.	Total n=75 Participants Total of all reporting groups
Age Continuous	36.1 years STANDARD_DEVIATION 2.5 • n=5 Participants	43.7 years STANDARD_DEVIATION 2.1 • n=7 Participants	43.2 years STANDARD_DEVIATION 2.5 • n=5 Participants	40.8 years STANDARD_DEVIATION 11.935 • n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	23 Participants n=7 Participants	24 Participants n=5 Participants	69 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Region of Enrollment United States	24 participants n=5 Participants	24 participants n=7 Participants	27 participants n=5 Participants	75 participants n=4 Participants
Body Mass Index	26.7 kg/m^2 STANDARD_DEVIATION 1.0 • n=5 Participants	29.7 kg/m^2 STANDARD_DEVIATION 1.1 • n=7 Participants	28.9 kg/m^2 STANDARD_DEVIATION 1.2 • n=5 Participants	28.3 kg/m^2 STANDARD_DEVIATION 5.5 • n=4 Participants

PRIMARY outcome

Timeframe: 1 hour after drug was ingested

Population: Intention-to-treat analysis

Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon.

After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)	17.57 mL/mm Hg Standard Error 0.935	16.2 mL/mm Hg Standard Error 1.03	18.76 mL/mm Hg Standard Error 1.13

SECONDARY outcome

Timeframe: 1 hour after ingestion of standard meal

Population: Intention-to-treat analysis

Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon.)

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Postprandial Change in Colonic Tone	30.34 mL Standard Error 4.76	27.41 mL Standard Error 3.35	26.31 mL Standard Error 4.81

SECONDARY outcome

Timeframe: 1 hour after drug was ingested

Population: Intention-to-treat analysis

The sensory threshold for first perception of pain was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Post-treatment Sensory Threshold for First Perception of Pain	42.83 mm Hg Standard Deviation 12.73	40.33 mm Hg Standard Deviation 17.17	44.44 mm Hg Standard Deviation 13.05

SECONDARY outcome

Timeframe: 1 hour after drug was ingested

Population: Intention-to-treat analysis

The sensory rating was measured by a 100 mm long Visual Analog Scale (VAS). The VAS does not have any pre-set marks between the extremes of 0 for no pain and 100 mm for extreme pain. The investigator measures the mark made by the participant in mm and records this for the value of pain.

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions 16 mm Hg Distension	38.18 mm Standard Error 4.68	38.71 mm Standard Error 4.64	37.0 mm Standard Error 4.57
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions 24 mm Hg Distension	49.64 mm Standard Error 5.83	42.75 mm Standard Error 5.16	39.76 mm Standard Error 5.06
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions 32 mm Hg Distension	58.36 mm Standard Error 5.14	45.35 mm Standard Error 4.83	46.76 mm Standard Error 4.78
Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions 40 mm Hg Distension	57.18 mm Standard Error 5.42	48.17 mm Standard Error 4.97	45.52 mm Standard Error 4.44

SECONDARY outcome

Timeframe: After 12 hour fast, before drug administered

Population: Intention-to-treat analysis

Colonic tone is a measurement of the volume of the colon. Colonic tone was assessed by noting the changes in the balloon volume in the presence of a constant operating pressure in the balloon (in the barostat-manometric assembly placed in the colon.)

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=24 Participants One dose of placebo will be taken orally with water.
Fasting Colonic Tone	117.8 mL Standard Error 7.97	118.5 mL Standard Error 6.41	114.3 mL Standard Error 5.50

SECONDARY outcome

Timeframe: 1 hour after ingestion of standard meal

Population: Intention-to-treat analysis

Colonic phasic pressure activity is summarized as a motility index (MI)=log_e[number of contractions * sum of amplitudes) + 1]. A normal fasting average motility index (MI) would be about 12. An increase in MI means an increase in the phasic contractions (in contrast to tone) which is measured as a change in volume of the barostat balloon. (Therefore, an increase in MI means that the meal is moving more quickly through the colon.)

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Postprandial Colonic Motility Index Proximal descending colon	11.24 log mm Hg Standard Deviation 1.13	11.22 log mm Hg Standard Deviation 1.56	10.70 log mm Hg Standard Deviation 2.51
Postprandial Colonic Motility Index Distal descending colon	9.97 log mm Hg Standard Deviation 2.8	10.23 log mm Hg Standard Deviation 1.92	10.50 log mm Hg Standard Deviation 1.69

SECONDARY outcome

Timeframe: 1 hour after drug was ingested

Population: Intention-to-treat analysis

The sensory threshold for first sensation was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Post-treatment Sensory Threshold for First Sensation	15.83 mm Hg Standard Deviation 9.62	15.5 mm Hg Standard Deviation 11.46	18.37 mm Hg Standard Deviation 14.65

SECONDARY outcome

Timeframe: 1 hour after drug was ingested

Population: Intention-to-treat analysis

The sensory threshold for first perception of gas was measured by stepwise inflation in increments of 4 mm Hg at 60 second intervals up to a maximum pressure of 64 mm Hg. During this assessment participants were asked to report when they had the first sensation. The investigator recorded the threshold pressure at which the participants reported this sensation.

Outcome measures

Measure	Dronabinol 2.5 mg n=24 Participants One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 Participants One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 Participants One dose of placebo will be taken orally with water.
Post-Treatment Sensory Threshold for First Perception of Gas	28.83 mm Hg Standard Deviation 17.57	27.33 mm Hg Standard Deviation 17.36	29.04 mm Hg Standard Deviation 16.81

Adverse Events

Dronabinol 2.5 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Dronabinol 5 mg

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Dronabinol 2.5 mg n=24 participants at risk One dose of dronabinol 2.5 mg will be taken orally with water.	Dronabinol 5 mg n=24 participants at risk One dose of dronabinol 5 mg will be taken orally with water.	Placebo n=27 participants at risk One dose of placebo will be taken orally with water.
General disorders Drowsy/tired	20.8% 5/24 • Number of events 5	29.2% 7/24 • Number of events 7	18.5% 5/27 • Number of events 5
General disorders Flushing/hot	25.0% 6/24 • Number of events 6	16.7% 4/24 • Number of events 4	14.8% 4/27 • Number of events 4
General disorders Headache	16.7% 4/24 • Number of events 4	8.3% 2/24 • Number of events 2	14.8% 4/27 • Number of events 4
General disorders Dizzy/light-headed	8.3% 2/24 • Number of events 2	20.8% 5/24 • Number of events 5	3.7% 1/27 • Number of events 1
General disorders Loopy/foggy thinking	8.3% 2/24 • Number of events 2	25.0% 6/24 • Number of events 6	0.00% 0/27
Cardiac disorders Elevated heart rate	8.3% 2/24 • Number of events 2	4.2% 1/24 • Number of events 1	18.5% 5/27 • Number of events 5

Additional Information

Dr. Michael Camilleri

Mayo Clinic

Phone: 507-266-2306

Email: camilleri.michael@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place