Hepatic EncephalopathyPhase 4NCT05788627
Effectiveness of Oral Lactulose Versus Lactulose Enema in Hepatic Encephalopathy
A Phase 4 study testing Tap water and Lactulose in people with Hepatic Encephalopathy and Chronic Liver Disease, run by Khyber Medical College, Peshawar.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy, Chronic Liver Disease
- What is being tested?
- Tap water and Lactulose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Apr 2023to Nov 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Patients with dehydration
- Electrolyte abnormalities
- Spontaneous bacterial peritonitis (SBP),
- Fever
- Using sedative / hypnotic medications as predisposing factors for hepatic encephalopathy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effectiveness Of Oral Lactulose Versus Lactulose Enema On The Time To Recovery From Overt Hepatic Encephalopathy
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.
Read the 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.
- Conditions
- Hepatic Encephalopathy, Chronic Liver Disease
- Being tested
- Tap water, Lactulose
- Medical subject headings
- Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tap waterDrug
Also called tap water enema
Oral lactulose in a dose of 30ml BD and tap water enema 1000ml BD
LactuloseDrug
Also called Lactulose enema
Oral lactulose in a dose of 30ml BD and lactulose enema (300ml lactulose and 700ml water) in a dose of 1000ml BD.
| Study group | Role | What they receive |
|---|---|---|
| Placebo arm / tap water enema arm | Placebo comparator | 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. Receives: Drug: Tap water |
| Lactulose enema arm | Experimental | This arm will receive oral lactulose in a dose of 30ml twice daily alongwith lactulose enema (300ml lactulose plus 700ml water) twice daily. Receives: Drug: Lactulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in grade of hepatic encephalopathy
Change in HE grade from grade 4 to grade 3 or grade 3 to grade 2
Measured: Over 48 hours
Secondary outcomes (1)
Relief of constipation
Frequency of 2-3 soft stools per 24 hours
Measured: Over 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2023
- Study startApr 2023 (estimated)
- Primary completionSep 2023 (estimated)
- Study completionNov 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Khyber Medical College, Peshawar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aliena Badshah, Principal investigator, Khyber Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05788627
- Sponsor's protocol ID
- 700
- Status last verified
- Apr 2023
- First submitted
- 14 Mar 2023
- Last updated
- 5 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Patients confidentiality shall be maintained at all stages. Other patient characteristics e.g grade of encephalopathy, serum ammonia levels before and after initiation of intervention, response to lactulose enema can be shared if required.
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness Of Oral Lactulose Versus Lactulose Enema On The Time To Recovery From Overt Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT05788627
- Acronym / sponsor ID
- 700
- Conditions
- Hepatic Encephalopathy, Chronic Liver Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Khyber Medical College, PeshawarUniversity, hospital or other
- Study start
- Apr 2023 (estimated)
- Primary completion
- Sep 2023 (estimated)
- Study completion
- Nov 2023 (estimated)
- First posted
- 29 Mar 2023 (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.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo arm / tap water enema arm | Placebo comparator | Drug: Tap waterThis 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. |
| Lactulose enema arm | Experimental | Drug: LactuloseThis arm will receive oral lactulose in a dose of 30ml twice daily alongwith lactulose enema (300ml lactulose plus 700ml water) twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- Patients with dehydration
- Electrolyte abnormalities
- Spontaneous bacterial peritonitis (SBP),
- Fever
- Using sedative / hypnotic medications as predisposing factors for hepatic encephalopathy
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 |
|---|---|---|
| Tap waterAlso: tap water enemaOral lactulose in a dose of 30ml BD and tap water enema 1000ml BD | Drug | Placebo arm / tap water enema arm |
| LactuloseAlso: Lactulose enemaOral lactulose in a dose of 30ml BD and lactulose enema (300ml lactulose and 700ml water) in a dose of 1000ml BD. | Drug | Lactulose enema arm |
Primary outcome
Change in grade of hepatic encephalopathy
Time frame: Over 48 hours
Change in HE grade from grade 4 to grade 3 or grade 3 to grade 2
1 secondary outcome
Relief of constipation
Time frame: Over 48 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2023.
- Individual participant dataSharing planned: Yes. Patients confidentiality shall be maintained at all stages. Other patient characteristics e.g grade of encephalopathy, serum ammonia levels before and after initiation of intervention, response to lactulose enema can be shared if required.
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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.
Aliena Badshah principal investigator
Khyber Medical College
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tap water and Lactulose in people with Hepatic Encephalopathy and Chronic Liver Disease, run by Khyber Medical College, Peshawar.
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 2 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aliena Badshah (0092-335-5950615, aliena.badshah@kmc.edu.pk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in grade of hepatic encephalopathy (time frame: Over 48 hours). 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 5 Apr 2023.