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Efficacy of Sildenafil in the Improvement of Cognition and Quality of Life in Patients With Cirrhosis of Liver. A Proof of Concept Study.

Primary Purpose

Hepatic Encephalopathy.

Status
Unknown status
Phase
Phase 1
Locations
India
Study Type
Interventional
Intervention
Sildenafil.
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Encephalopathy. focused on measuring Minimal Hepatic Encephalopathy (MHE), Psychometric Hepatic Encephalopathy Score (PHES), Sickness Impact Profile (SIP), Model for End-stage Liver Disease (MELD), Child-Turcotte-Pugh score (CTP)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: • Male patients aged 18-70 years diagnosed to have cirrhosis of liver at Liver Clinic of Department of Hepatology, PGIMER Chandigarh by means of clinical, biochemical and ultrasonographical/CT or liver biopsy.

  • MHE will be defined by PHES ≤-5 and normal MMSE score of ≥24.

Exclusion Criteria:

  • Patients unable to give informed consent.
  • H/O alcohol intake during last 12 weeks.
  • Significant comorbid illness such as heart disease, respiratory disease, or renal failure.
  • Any neurological disease such as Alzheimer disease, Parkinson's disease, stroke, non- hepatic metabolic encephalopathy's.
  • Any anatomical deformities or disease of the penis such as Peyronie's disease.
  • Patients having psychiatric illness and taking treatment with antidepressant, sedative or neuroleptics.
  • Patients who start taking alcohol during the study period will be excluded.
  • Patients taking vasodilators such as nitrates.
  • Hepatocellular carcinoma.
  • Recent history of upper GI bleed in last 6 weeks.
  • Active ongoing infection.
  • Electrolyte abnormality precipitating MHE.
  • Color vision abnormalities.

Sites / Locations

  • Postgraduate Institute of Medical Education & Research Chandigarh

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention 'Sildenafil'.

'No sildenafil'

Arm Description

MHE patient receiving Sildenafil. Intervention: Sildenafil Drug Dosage: 25 mg once a day for one week followed by 25 mg twice daily for two weeks then 25 mg thrice daily for one week.

Control Arm: MHE patients not receiving SIldenafil Intervention.Followed up for 4 weeks.

Outcomes

Primary Outcome Measures

Cognition( PHES)
Improvement of impairment in cognition as assessed by PHES (Psychometric Hepatic Encephalopathy Score) in patients of MHE (Minimal hepatic Encephalopathy) by means of pharmacological intervention by sildenafil (a PDE-5 inhibitor) before and after treatment.
QOL(SIP)
To study the impact of treatment with sildenafil administration on the improvement in health-related quality-of-life of patients as assessed by sickness impact profile (SIP) before and after treatment.

Secondary Outcome Measures

CTP and MELD score before and after treatment with Sildenafil.
To study the impact of treatment with sildenafil on CTP and MELD scores before and after treatment.
Blood Ammonia and Interleukin-6 levels before and after treatment with Sildenafil.
Blood Ammonia and Interleukin-6 levels before and after treatment.

Full Information

First Posted
December 28, 2013
Last Updated
January 3, 2014
Sponsor
Postgraduate Institute of Medical Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT02028429
Brief Title
Efficacy of Sildenafil in the Improvement of Cognition and Quality of Life in Patients With Cirrhosis of Liver. A Proof of Concept Study.
Official Title
To Study The Proof of Concept in The Improvement of Cognition and Quality of Life in Cirrhotic Patients With Minimal Hepatic Encephalopathy by Means of a Pharmacological Intervention With Sildenafil (A Phosphodiesterase-5 Inhibitor).
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Unknown status
Study Start Date
July 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
January 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study is being conducted to evaluate the efficacy of Sildenafil (a 5-phosphodiesterase inhibitor) as a means to improve the cognitive impairment encountered in patients of minimal hepatic encephalopathy (MHE) as proposed in different studies. This study would also assess the role of improvement of cognition as a means of improvement in quality of life.The patients will receive Sildenafil or no treatment for 4 weeks. This study may prove and provide important therapeutic strategy for cognition impairment in patients with MHE.
Detailed Description
Primary Aim To study the proof of concept in the improvement of impairment in cognition as assessed by PHES (psychometric hepatic encephalopathy score) in patients of MHE by means of pharmacological intervention by Sildenafil (a phosphodiesterase(PDE)-5 inhibitor) before and after treatment. To study the impact of treatment with Sildenafil administration on the improvement in health-related quality-of-life of patients as assessed by Sickness impact profile (SIP) before and after treatment. Secondary Aim To study the impact of treatment with Sildenafil on CTP and MELD scores before and after treatment. To study the impact of treatment with Sildenafil on blood ammonia and Interleukin-6 levels before and after treatment. Study Population: The study population comprises of male adult (age 18-70 years) with cirrhosis of liver. Patients with cirrhosis of liver have been divided into two groups - with MHE and without or no MHE (NMHE) based on the test result of PHES, i.e., abnormal (MHE group) or normal (NMHE group). Inclusion Criteria: Male patients aged 18-70 years diagnosed to have cirrhosis of liver at Liver Clinic of Department of Hepatology, Postgraduate Institute of Medical Education & Research(PGIMER), Chandigarh by means of clinical, biochemical and ultrasonographical/CT or liver biopsy. MHE will be defined by PHES ≤-5 and normal Mini-Mental State Examination (MMSE) score of ≥24. Exclusion Criteria: Patients unable to give informed consent. H/O alcohol intake during last 12 weeks. Significant comorbid illness such as heart disease, respiratory disease, or renal failure. Any neurological disease such as Alzheimer disease, Parkinson's disease, stroke, non- hepatic metabolic encephalopathy's. Any anatomical deformities or disease of the penis such as Peyronie's disease. Patients having psychiatric illness and taking treatment with antidepressant, sedative or neuroleptics. Patients who start taking alcohol during the study period will be excluded. Patients taking vasodilators such as nitrates. Hepatocellular carcinoma. Recent history of upper GI bleed in last 6 weeks. Active ongoing infection. Electrolyte abnormality precipitating MHE. Color vision abnormalities.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy.
Keywords
Minimal Hepatic Encephalopathy (MHE), Psychometric Hepatic Encephalopathy Score (PHES), Sickness Impact Profile (SIP), Model for End-stage Liver Disease (MELD), Child-Turcotte-Pugh score (CTP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention 'Sildenafil'.
Arm Type
Experimental
Arm Description
MHE patient receiving Sildenafil. Intervention: Sildenafil Drug Dosage: 25 mg once a day for one week followed by 25 mg twice daily for two weeks then 25 mg thrice daily for one week.
Arm Title
'No sildenafil'
Arm Type
No Intervention
Arm Description
Control Arm: MHE patients not receiving SIldenafil Intervention.Followed up for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Sildenafil.
Other Intervention Name(s)
Suhagra.
Intervention Description
Arm 1 :Sildenafil Drug Dosage: 25 mg once a day for one week followed by 25 mg twice daily for two weeks then 25 mg thrice daily for one week.
Primary Outcome Measure Information:
Title
Cognition( PHES)
Description
Improvement of impairment in cognition as assessed by PHES (Psychometric Hepatic Encephalopathy Score) in patients of MHE (Minimal hepatic Encephalopathy) by means of pharmacological intervention by sildenafil (a PDE-5 inhibitor) before and after treatment.
Time Frame
4 weeks
Title
QOL(SIP)
Description
To study the impact of treatment with sildenafil administration on the improvement in health-related quality-of-life of patients as assessed by sickness impact profile (SIP) before and after treatment.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
CTP and MELD score before and after treatment with Sildenafil.
Description
To study the impact of treatment with sildenafil on CTP and MELD scores before and after treatment.
Time Frame
4 weeks
Title
Blood Ammonia and Interleukin-6 levels before and after treatment with Sildenafil.
Description
Blood Ammonia and Interleukin-6 levels before and after treatment.
Time Frame
4 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • Male patients aged 18-70 years diagnosed to have cirrhosis of liver at Liver Clinic of Department of Hepatology, PGIMER Chandigarh by means of clinical, biochemical and ultrasonographical/CT or liver biopsy. MHE will be defined by PHES ≤-5 and normal MMSE score of ≥24. Exclusion Criteria: Patients unable to give informed consent. H/O alcohol intake during last 12 weeks. Significant comorbid illness such as heart disease, respiratory disease, or renal failure. Any neurological disease such as Alzheimer disease, Parkinson's disease, stroke, non- hepatic metabolic encephalopathy's. Any anatomical deformities or disease of the penis such as Peyronie's disease. Patients having psychiatric illness and taking treatment with antidepressant, sedative or neuroleptics. Patients who start taking alcohol during the study period will be excluded. Patients taking vasodilators such as nitrates. Hepatocellular carcinoma. Recent history of upper GI bleed in last 6 weeks. Active ongoing infection. Electrolyte abnormality precipitating MHE. Color vision abnormalities.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Radha K Dhiman, MD, DM, FACG
Organizational Affiliation
PGIMER Chandigarh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Postgraduate Institute of Medical Education & Research Chandigarh
City
Chandigarh
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

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Efficacy of Sildenafil in the Improvement of Cognition and Quality of Life in Patients With Cirrhosis of Liver. A Proof of Concept Study.

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