Cannabis Hyperemesis SyndromePhase 4HALONCT04176055
Treatment Strategies in CHS
A Phase 4 study testing Haloperidol in people with Cannabis Hyperemesis Syndrome, run by University of Calgary at 1 site in Canada.
Trial summary
Background: In the gastrointestinal (GI) system, the most well-described manifestation of prolonged cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic nausea and vomiting and associated with abdominal pain.Currently, the generally accepted management for CHS is complete… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cannabis Hyperemesis Syndrome
- What is being tested?
- Haloperidol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteCanada
- Study dates
- 13 Oct 2020to 1 Jun 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completed Baseline study prior to enrollment
- Age ≥ 18 years and ≤ 65 years
- Gastrointestinal symptomology as measured by GCSI > 2 or PAGI-SYM > 2 (upper or lower abdominal pain subscale)
- Ongoing cannabis use (> 1g/wk)
- Resident of Alberta with valid Alberta Health Care number
Who cannot join
- Pregnancy and/or breastfeeding
- Corrected QT interval measured on ECG > 450 ms for males or >470 ms for females
- History of seizure, venous thromboembolism (VTE), psychosis, Parkinson's disease or spastic disorder
- Concurrent diagnosis of or suspected gastroparesis or functional dyspepsia
- Diabetes with neuropathy.
- Any gastrointestinal, neurological, or other illness felt by the investigators to be potentially involved in symptom generation or pose a safety risk to inclusion in this study.
- Previous gastric or intestinal surgery which may lead to symptoms
- Use of concomitant medications which cannot be stopped for the 4-week haloperidol phase of the study: including narcotics, antihistamines such as diphenhydramine (Benadryl) or dimenhydrinate (Gravol), dopamine antagonists (domperidone, metoclopramide, risperidone, clozapine, quetiapine), macrolide antibiotics, prokinetics (prucalopride), tricyclic antidepressants (TCA) at doses >50 mg, barbiturates, 5HT3 antagonists (ondansetron).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Evaluation of Symptoms and Open Label Haloperidol in Cannabinoid Hyperemesis Syndrome (HALO)
Background:
In the gastrointestinal (GI) system, the most well-described manifestation of prolonged cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic nausea and vomiting and associated with abdominal pain.Currently, the generally accepted management for CHS is complete cannabis abstinence as traditional anti-emetics appear to be minimally effective. Preliminary reports from emergency departments suggest that intravenous haloperidol, a typical anti- psychotic, provides effective symptomatic relief in CHS.
Read more
Objective:
- To learn more about how cannabis use relates to the management of CHS.
- To learn if haloperidol is effective in treating the symptoms of CHS.
Eligibility:
Alberta residents with ongoing cannabis use, who have completed the baseline study, are ≥ 18 years and ≤ 65 years, and have gastrointestinal symptomology as measured by GCSI > 2 or PAGI-SYM > 2 (upper or lower abdominal pain subscale).
Design:
Participants will answer a series of questionnaires online. Study specific questions relating to symptoms, cannabis use, and anxiety and depression will be administered. Confirmation of cannabis cessation will be assessed with urine creatinine and cannabis metabolite measures. Salivary cortisol will be used to asses the stress response.
Read the detailed description
In the gastrointestinal (GI) system, the most well-described manifestation of prolonged cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic nausea and vomiting and associated with abdominal pain.The pathophysiology of CHS is poorly understood but may involve alterations gut motility and/or activation of the hypothalamic-pituitary-adrenal (HPA) axis.
Our endogenous endocannabinoid system contains the cannabinoid receptor type I (CB1) and type II (CB2), and their ligands, anandamide (AEA) and 2-arachidonylglycerol (2-AG). CB1 receptors are widely distributed throughout the central and peripheral nervous system, including the myenteric plexus of the GI tract. In humans, oral Δ9-THC (an active cannabis compound) reduces gastric emptying and patients with slow transit constipation have increased expression of endogenous endocannabinoids and higher CB1 receptor expression. In CHS, chronic cannabis use may cause significant activation of peripheral, gut-located CB1.
The hypothalamic-pituitary- adrenal (HPA) axis, the main neuroendocrine system activated in response to stressful stimuli may also be involved in CHS. Activation of centrally located CB1 receptors by 2-AG plays a crucial role in down-regulating the HPA axis in recovery from stress. Reduction in 2-AG activity within the hypothalamus by stress, leads to reduced hypothalamic CB1 receptor activation; this reduced CB1 activation is also observed in prolonged cannabis use.
Currently, the generally accepted management for CHS is complete cannabis abstinence as traditional anti-emetics appear to be minimally effective.Preliminary reports from emergency departments suggest that intravenous haloperidol, a typical anti- psychotic, provides effective symptomatic relief and has become a first-line agent for acute CHS.
Outcome measures:
The primary endpoints will look at the correlation between quantitative weekly cannabis use and gastrointestinal symptoms at week 8 and the mean change of the GI symptoms from week 8 to week 12 during.
- Conditions
- Cannabis Hyperemesis Syndrome
- Being tested
- Haloperidol
- Medical subject headings
- Cannabinoid Hyperemesis Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HaloperidolDrug
haloperidol intervention
| Study group | Role | What they receive |
|---|---|---|
| HALO | Experimental | Not described Receives: Drug: Haloperidol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between quantitative weekly cannabis use and GI symptoms at week 8
GI symptoms will be measured PAGI-SYM, a 20-item Likert-type measure with six sub classes. Cannabis use will be measured by the cannabis consumption inventory (DFAQ-CU).The participants will fill out the questionnaires every 2 weeks.
Measured: 1st 8 weeks of the 12 week study for outcome 1
Mean change in GI symptoms from week 8 to week 12
GI symptoms will be measured PAGI-SYM, a 20-item Likert-type measure with six sub classes. The participants will fill out the questionnaire every 2 weeks.
Measured: final 4 weeks of the 12 week study for outcome 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2019
- Study start13 Oct 2020
- Primary completion1 Jun 2021
- Study completion1 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis Hyperemesis SyndromeStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Christopher Andrews, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04176055
- Sponsor's protocol ID
- REB19-1197
- Acronym
- HALO
- Status last verified
- Aug 2022
- First submitted
- 20 Nov 2019
- Last updated
- 10 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Symptoms and Open Label Haloperidol in Cannabinoid Hyperemesis Syndrome (HALO)
- ClinicalTrials.gov ID
- NCT04176055
- Acronym / sponsor ID
- HALO / REB19-1197
- Conditions
- Cannabis Hyperemesis Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 25 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
In the gastrointestinal (GI) system, the most well-described manifestation of prolonged cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic nausea and vomiting and associated with abdominal pain.Currently, the generally accepted management for CHS is complete cannabis abstinence as traditional anti-emetics appear to be minimally effective. Preliminary reports from emergency departments suggest that intravenous haloperidol, a typical anti- psychotic, provides effective symptomatic relief in CHS.
Objective:
- To learn more about how cannabis use relates to the management of CHS.
- To learn if haloperidol is effective in treating the symptoms of CHS.
Eligibility:
Alberta residents with ongoing cannabis use, who have completed the baseline study, are ≥ 18 years and ≤ 65 years, and have gastrointestinal symptomology as measured by GCSI > 2 or PAGI-SYM > 2 (upper or lower abdominal pain subscale).
Design:
Participants will answer a series of questionnaires online. Study specific questions relating to symptoms, cannabis use, and anxiety and depression will be administered. Confirmation of cannabis cessation will be assessed with urine creatinine and cannabis metabolite measures. Salivary cortisol will be used to asses the stress response.
Detailed description
In the gastrointestinal (GI) system, the most well-described manifestation of prolonged cannabis use is cannabinoid hyperemesis syndrome (CHS). CHS is characterized by severe cyclic nausea and vomiting and associated with abdominal pain.The pathophysiology of CHS is poorly understood but may involve alterations gut motility and/or activation of the hypothalamic-pituitary-adrenal (HPA) axis.
Our endogenous endocannabinoid system contains the cannabinoid receptor type I (CB1) and type II (CB2), and their ligands, anandamide (AEA) and 2-arachidonylglycerol (2-AG). CB1 receptors are widely distributed throughout the central and peripheral nervous system, including the myenteric plexus of the GI tract. In humans, oral Δ9-THC (an active cannabis compound) reduces gastric emptying and patients with slow transit constipation have increased expression of endogenous endocannabinoids and higher CB1 receptor expression. In CHS, chronic cannabis use may cause significant activation of peripheral, gut-located CB1.
The hypothalamic-pituitary- adrenal (HPA) axis, the main neuroendocrine system activated in response to stressful stimuli may also be involved in CHS. Activation of centrally located CB1 receptors by 2-AG plays a crucial role in down-regulating the HPA axis in recovery from stress. Reduction in 2-AG activity within the hypothalamus by stress, leads to reduced hypothalamic CB1 receptor activation; this reduced CB1 activation is also observed in prolonged cannabis use.
Currently, the generally accepted management for CHS is complete cannabis abstinence as traditional anti-emetics appear to be minimally effective.Preliminary reports from emergency departments suggest that intravenous haloperidol, a typical anti- psychotic, provides effective symptomatic relief and has become a first-line agent for acute CHS.
Outcome measures:
The primary endpoints will look at the correlation between quantitative weekly cannabis use and gastrointestinal symptoms at week 8 and the mean change of the GI symptoms from week 8 to week 12 during.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HALO | Experimental | Drug: Haloperidol |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Completed Baseline study prior to enrollment
- Age ≥ 18 years and ≤ 65 years
- Gastrointestinal symptomology as measured by GCSI > 2 or PAGI-SYM > 2 (upper or lower abdominal pain subscale)
- Ongoing cannabis use (> 1g/wk)
- Resident of Alberta with valid Alberta Health Care number
Key exclusion criteria (8 listed)
- Pregnancy and/or breastfeeding
- Corrected QT interval measured on ECG > 450 ms for males or >470 ms for females
- History of seizure, venous thromboembolism (VTE), psychosis, Parkinson's disease or spastic disorder
- Concurrent diagnosis of or suspected gastroparesis or functional dyspepsia
- Diabetes with neuropathy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haloperidolhaloperidol intervention | Drug | HALO |
Primary outcome
Correlation between quantitative weekly cannabis use and GI symptoms at week 8
Time frame: 1st 8 weeks of the 12 week study for outcome 1
GI symptoms will be measured PAGI-SYM, a 20-item Likert-type measure with six sub classes. Cannabis use will be measured by the cannabis consumption inventory (DFAQ-CU).The participants will fill out the questionnaires every 2 weeks.
Mean change in GI symptoms from week 8 to week 12
Time frame: final 4 weeks of the 12 week study for outcome 2
GI symptoms will be measured PAGI-SYM, a 20-item Likert-type measure with six sub classes. The participants will fill out the questionnaire every 2 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2022.
Related trials for Cannabis Hyperemesis Syndrome
Enrolling by invitationObservational study
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Not yet recruitingEarly Phase 1
Haloperidol For Outpatient Symptom Management in Patients Diagnosed With Cannabinoid Hyperemesis Syndrome in the Emergrency Department
Cannabinoid Hyperemesis Syndrome
RecruitingObservational study
Cannabinoid Hyperemesis Syndrome. Prospective Multicenter Study of Patients Admitted to Adult Emergency Departments in Maine-et-Loire.
D000096704, Cannabinoid Hyperemesis Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Haloperidol in people with Cannabis Hyperemesis Syndrome, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between quantitative weekly cannabis use and GI symptoms at week 8 (time frame: 1st 8 weeks of the 12 week study for outcome 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2022.