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Does ALlopurinol Regress lefT Ventricular Hypertrophy in End Stage REnal Disease: The ALTERED Study (Altered)

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ClinicalTrials.gov Identifier: NCT01951404
Recruitment Status : Completed
First Posted : September 26, 2013
Last Update Posted : November 4, 2016
Sponsor:
Collaborators:
British Heart Foundation
NHS Tayside
NHS Greater Glasgow and Clyde
University of Glasgow
Information provided by (Responsible Party):
Elaine Rutherford, University of Dundee

Brief Summary:

Kidney patients on dialysis commonly die because of heart disease. One of the biggest problems in their hearts is that the muscle wall of the heart thickens. This makes it less efficient. We found in patients with mild kidney disease that a drug normally used to treat gout (allopurinol) had the remarkable side effect of being able to reduce this thickening of their heart wall. In this new study we aim to find out if this benefit of allopurinol also occurs in severe kidney patients i.e. those on regular dialysis. We also are trying to figure out the best dose of allopurinol to use. To do this we are planning a study where we will recruit patients with kidney disease who are on dialysis. The 1st phase of the trial will be to determine the best dose of allopurinol to use and the second phase will be to do a clinical trial where patients will be randomly allocated to either this optimum dose of allopurinol or a dummy medication (placebo) and will receive one year of treatment. They will have a special scan of the heart using an MRI machine to measure the extent of thickening of their heart muscle before they start on treatment and will have a further MRI scan when their one year treatment finishes.

Phase 1- the dose finding study, will involve 10 patients who will have between 3 and 7 visits to the hospital scheduled around 4 to 17 dialysis sessions. The later study will involve up to 76 patients who will be asked to attend the hospital up to 8 times over a 13 month period.


Condition or disease Intervention/treatment Phase
End Stage Renal Disease Left Ventricular Hypertrophy Drug: Allopurinol Drug: Placebo (for allopurinol) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does ALlopurinol Regress lefT Ventricular Hypertrophy in End Stage REnal Disease: The ALTERED Study
Study Start Date : September 2013
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Allopurinol
Participants in this arm will be given allopurinol with the dose gradually increasing weekly as tolerated up to the dose determined in the first phase of the study. The drug dose will be given orally 3 times weekly after dialysis for 1 year.
Drug: Allopurinol
Placebo Comparator: Placebo
Participants in this arm will be given placebo with the dose appearing to gradually increase weekly as tolerated up to the dose determined in the first phase of the study. The drug dose will be given orally 3 times weekly after dialysis for 1 year.
Drug: Placebo (for allopurinol)



Primary Outcome Measures :
  1. The primary outcome is to measure if allopurinol, induces a change in Left ventricular Mass Index in patients with ESRD when compared to placebo. [ Time Frame: following 1 year of therapy ]

Secondary Outcome Measures :
  1. To decide on optimum dosing regime of allopurinol in End Stage Renal Disease from pilot study [ Time Frame: 6 weeks ]
    The dose of allopurinol required to reduce urate levels by 41% will be determined.

  2. To measure any difference in endothelial function with allopurinol compared with placebo, measured by Flow Mediated Dilatation and Pulse Wave Analysis [ Time Frame: following 1 year of therapy ]
  3. To assess if the incidence of adverse events differs on allopurinol compared to placebo in patients with end stage renal disease [ Time Frame: during course of 1 year of therapy ]
  4. To measure any change in LV end systolic volume, LV end diastolic volume or LV ejection factor with allopurinol in ESRD patients compared with placebo. [ Time Frame: Following 1 year of therapy ]
  5. To measure changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo. [ Time Frame: Following 1 year of therapy ]
  6. To measure changes in BP control as measured by clinic BP and 24hr BP monitoring with allopurinol compared with placebo [ Time Frame: Following 1 year of therapy ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aged 18 years or over
  • end stage renal disease (CKD stage 5 eGFR <15ml/min /1.73m2)
  • been on haemodialysis for at least 3 months.

Exclusion Criteria:

  • Known heart failure
  • Left Ventricular Ejection Fraction <45%,
  • active gout
  • severe hepatic disease
  • or on azathioprine, 6 mercaptopurine, theophylline.
  • malignancy or other life threatening diseases,
  • pregnant or lactating women
  • any contraindication to MRI (claustrophobia, metal implants).
  • with a planned (relative) kidney transplant,
  • Patients who have participated in any other clinical trial within the previous 30 days will be excluded.
  • Patients who are unable to give informed consent will also be excluded from this trial.
  • Any other considered by a study physician to be inappropriate for inclusion

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951404


Locations
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United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, La, United Kingdom, G12 8TA
NHS Tayside
Dundee, Tayside, United Kingdom, DD9 1SY
NHS Ayrshire and Arran
Crosshouse, United Kingdom, KA2OBE
Sponsors and Collaborators
University of Dundee
British Heart Foundation
NHS Tayside
NHS Greater Glasgow and Clyde
University of Glasgow
Investigators
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Study Director: Allan D Struthers, BSc, MD, FRCP, FESC, FRSE Centre for Cadiovascular Medicine, University of Dundee

Publications:
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Responsible Party: Elaine Rutherford, Clinical Research Fellow - Principal Investigator, University of Dundee
ClinicalTrials.gov Identifier: NCT01951404     History of Changes
Other Study ID Numbers: 2012CV07
First Posted: September 26, 2013    Key Record Dates
Last Update Posted: November 4, 2016
Last Verified: November 2016

Keywords provided by Elaine Rutherford, University of Dundee:
Left Ventricular Hypertrophy
Allopurinol
End Stage Renal Disease
Haemodialysis
Renal Replacement Therapy
MRI

Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Hypertrophy
Hypertrophy, Left Ventricular
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Pathological Conditions, Anatomical
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Allopurinol
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs