Clinical trial NCT02165488: Frequent Ketamine Use and Gastrointestinal, Liver and Biliary Sequelae
Official title: Gastrointestinal, Hepatic and Biliary Sequelae of Frequent Ketamine Use: a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastritis
Peptic Ulcer Disease
Cholangiopathy
Liver Fibrosis
Keywords: ketamine
abuse
abdominal discomfort
cholangiopathy
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2014-06-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recreational use of ketamine with frequency at least twice per month over 6 months within the last 2 years, with or without other illicit psychotropic drug.

Brief summary: 30% of ketamine users complain of abdominal discomfort. Long-term ketamine use is associated with hepatotoxicity and pathologic changes to the biliary tract. Yet the prevalence of gastrointestinal and hepatobiliary pathologies in ketamine users has not been well-described. The investigators plan to recruit a large number of ketamine users based on referrals from different Psychiatry clusters in Hong Kong and to investigate the underlying cause of abdominal discomfort, describe the prevalence of different gastrointestinal and hepatobiliary pathologies and describe their long-term outcome.

Detailed description: The recreational use of psychotropic drugs has been increasing over the past 2 decades in Hong Kong. Ketamine hydrochloride is currently one of the most popular recreational drugs in Hong Kong, and its recreational use is also increasing in the United Kingdom and Europe. Inhalation of ketamine could result in hallucinations, out-of-the-body experiences and psychological dissociation, making it popular among young adults. One of the well-known side effects of ketamine is bladder dysfunction, which is seen in one-quarter of chronic ketamine users .

Ketamine has also been known to be associated with gastrointestinal symptoms. Colicky epigastric / abdominal discomfort in ketamine users, known as "K-cramps", has been reported in 33.3% of frequent ketamine users, and is the second-most common symptom of presentation (21%) among ketamine users in the emergency department . Nonetheless, the underlying etiology resulting in this abdominal discomfort remains poorly defined. A possible etiology is intestinal motility disorders, since ketamine interferes with gastric motility. Another possible cause could be ketamine-related cholangiopathy, which has been described in both Asia and Western countries. Another possible cause could be ketamine-related liver dysfunction, which is seen in 16% of ketamine users. Chronic ketamine hepatotoxicity is associated with mitochondrial liver injury , and could result in bridging liver fibrosis.

We plan to recruit subjects from ketamine users seeking medical attention at substance abuse clinics in different psychiatric clusters in Hong Kong. A screening log will be kept on the total number of ketamine users attending different substance abuse clinics and the number of potential subjects referred to our center.

Baseline sociodemographic information will be obtained. A standardized method will be used to assess and quantify the degree of ketamine use, as well as the recreational use of other psychotropic drugs (e.g. ecstasy, methamphetamine, marijuana etc.) and alcohol intake. Subjects will then be assessed for the presence or absence of dyspepsia, biliary-type abdominal pain， gastroparesis or other abdominal symptoms following standard criteria.

Eligibility criteria: Inclusion Criteria:

* Use of ketamine or ketamine mixed with other psychotropic drugs with frequency of at least twice per month over 6 months within the last 2 years.
* Recurrent abdominal discomfort over the past 3 months or more.
* Han Chinese ethnicity.
* Age 18-60 years.

Exclusion Criteria:

* Mental retardation or unable to give informed consent
* Co-existing biliary disorders including recurrent pyogenic cholangitis, primary sclerosing cholangitis, IgG4 sclerosing cholangiopathy and HIV cholangiopathy.
* Other significant medical co-morbidities

Primary outcomes:
measure: Incidence of cholangiopathic changes
timeFrame: 3 months
measure: Incidence of peptic ulcer disease
timeFrame: 3 months
measure: Incidence of liver fibrosis
timeFrame: 3 months
Secondary outcomes:
measure: Long-term outcome of peptic ulcer disease in ketamine users
timeFrame: 24 months
measure: Long-term outcome of liver fibrosis in ketamine users
timeFrame: up to 24 months
measure: Long-term outcomes of cholangiopathic changes in ketamine users
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
Study officials:
References:
citation: Seto WK, Mak SK, Chiu K, Vardhanabhuti V, Wong HF, Leong HT, Lee PSF, Ho YC, Lee CK, Cheung KS, Yuen MF, Leung WK. Magnetic resonance cholangiogram patterns and clinical profiles of ketamine-related cholangiopathy in drug users. J Hepatol. 2018 Jul;69(1):121-128. doi: 10.1016/j.jhep.2018.03.006. Epub 2018 Mar 16.