Effectiveness of Oral Lactulose Versus Lactulose Enema in Hepatic Encephalopathy

Sponsor

Khyber Medical College, Peshawar (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05788627

Collaborator

(none)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Patients with chronic liver disease due to hepatitis B or C viruses, Non-alcoholic fatty liver disease, autoimmune hepatitis, wilson disease, cryptogenic hepatitis etc are prone to develop complications. Hepatic encephalopathy is one of such complications. It is graded into four types depending on severity of clinical features, which range through altered sleep pattern to coma. The current study aims to compare the effectiveness of lactulose enema with oral lactulose in time to recovery from higher grade of encephalopathy to lower grade of encephalopathy.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy Chronic Liver Disease	Drug: Tap water Drug: Lactulose	Phase 4

Detailed Description

Hepatic encephalopathy (HE) is defined as neuropsychiatric disorder due to liver failure. It is characterized by mild cognitive impairment, stupor and coma. The most common reasons for pathogenesis include the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. Neurotoxin ammonia is related to precipitating HE, for which the gastrointestinal tract is the primary source. Colonic bacteria catabolise the nitrogenous sources into ammonia.

Lactulose is the initial treatment for HE. It produces diarrhea by osmosis and reduces pH of colonic contents, which leads to reduced absorption of ammonia by converting it to ammonium ion (NH4). Understandingly, it does not cure the underlying liver disease however, it does prevent deterioration of the mental status in HE.

Initial oral dose of lactulose is 30 ml once a day or twice daily. For retention enema the dose is 300 ml lactulose plus 700 ml water, administered every 4 hours. It can be increased as tolerated. At least, 2-4 loose stools per day should be passed by the patient.

Lactulose is also effective as primary prophylaxis against the development of HE.

Constipation is one very common precipitating factor for hepatic encephalopathy which is routinely managed with oral lactulose or kleen enema (21.4g (18.1% w/v) Sodium Dihydrogen Phosphate Dihydrate and 9.4g (8.0% w/v) Disodium Phosphate Dodecahydrate). Lactulose enema is also given to patients in hepatic encephalopathy either alone or in combination with oral lactulose. However it is not clear whether there is any difference in the efficacy of oral or enema lactulose in patients with hepatic encephalopathy in terms of improvement of encephalopathy grade and time to improvement. This study aims to determine the efficacy of oral versus enema lactulose in the achievement of these goals.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Effectiveness Of Oral Lactulose Versus Lactulose Enema On The Time To Recovery From Overt Hepatic Encephalopathy

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo arm / tap water enema arm This arm will receive oral lactulose as per treatment protocol for hepatic encephalopathy i.e. 30ml twice daily. And will receive tap water enema as placebo i.e. 1000ml tap water enema twice daily.	Drug: Tap water Oral lactulose in a dose of 30ml BD and tap water enema 1000ml BD Other Names: tap water enema
Experimental: Lactulose enema arm This arm will receive oral lactulose in a dose of 30ml twice daily alongwith lactulose enema (300ml lactulose plus 700ml water) twice daily.	Drug: Lactulose Oral lactulose in a dose of 30ml BD and lactulose enema (300ml lactulose and 700ml water) in a dose of 1000ml BD. Other Names: Lactulose enema

Arm

Intervention/Treatment

Placebo Comparator: Placebo arm / tap water enema arm

This arm will receive oral lactulose as per treatment protocol for hepatic encephalopathy i.e. 30ml twice daily. And will receive tap water enema as placebo i.e. 1000ml tap water enema twice daily.

Drug: Tap water

Oral lactulose in a dose of 30ml BD and tap water enema 1000ml BD

Other Names:

tap water enema

Experimental: Lactulose enema arm

This arm will receive oral lactulose in a dose of 30ml twice daily alongwith lactulose enema (300ml lactulose plus 700ml water) twice daily.

Drug: Lactulose

Oral lactulose in a dose of 30ml BD and lactulose enema (300ml lactulose and 700ml water) in a dose of 1000ml BD.

Other Names:

Lactulose enema

Outcome Measures

Primary Outcome Measures

Change in grade of hepatic encephalopathy [Over 48 hours]
Change in HE grade from grade 4 to grade 3 or grade 3 to grade 2

Secondary Outcome Measures

Relief of constipation [Over 48 hours]
Frequency of 2-3 soft stools per 24 hours

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female cirrhotic patients in grades 3 or 4 of hepatic encephalopathy
Patient with constipation as the precipitating factor will be included in the study

Exclusion Criteria:

Patients with dehydration
Electrolyte abnormalities
Spontaneous bacterial peritonitis (SBP),
Fever
Using sedative / hypnotic medications as predisposing factors for hepatic encephalopathy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Khyber Medical College, Peshawar

Investigators

Principal Investigator: Aliena Badshah, Khyber Medical College

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Khyber Medical College, Peshawar

ClinicalTrials.gov Identifier:

NCT05788627

Other Study ID Numbers:

First Posted:

Mar 29, 2023

Last Update Posted:

Apr 5, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Liver Diseases

Hepatic Encephalopathy

Brain Diseases

Lactulose

Study Results

No Results Posted as of Apr 5, 2023