Clinical Trial: Does ALlopurinol Regress lefT Ventricular Hypertrophy in End Stage REnal Disease: The ALTERED Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Does ALlopurinol Regress lefT Ventricular Hypertrophy in End Stage REnal Disease: The ALTERED Study

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.


Detailed Summary:

The ALTERED trial is a randomised, double blinded, placebo controlled multi-centre study conducted in NHS Tayside, NHS Ayrshire & Arran & NHS Greater Glasgow & Clyde to compare allopurinol (dose to be confirmed from dose escalation study noted above) at either, 100mg, 200mg, 250mg, 300mg or 350mg to placebo.

Patients will be enrolled in this trial for a period of between 12 to 13 months.

At screening visit an initial history and clinical examination will be performed. Participants will then undergo an echocardiogram to ensure no significant heart failure unless they have had an ECHO in the previous 4 years..Should the participant be eligible for the study they will have a Cardiac Magnetic Resonance Imaging (MRI) scan prior to their baseline (Randomisation) visit. They will also have bloods taken for safety analysis, have a 12 lead ECG done, vital signs recorded and if they agree have 24 hour BP monitoring.

Once the patient is known to be eligible they will return - for the first randomisation, dosing visit at any time up to four weeks after screening. At this randomisation visit post dialysis session, eligible participants will be randomly assigned to either placebo or allopurinol 100mg.

They will continue on allopurinol/placebo 100mg for 2 weeks, with dosing after each dialysis session only. They can have FMD, PWV and PWA measurements taken. All participants will be offered the opportunity to opt in or out of the FMD, PWV and PWA measurements, which are secondary outcome measures only.

If study drugs are tolerated, the dose would be increased at weekly intervals after the 200mg dose to the allopurinol dose chosen by the dose escalation study, if greater than 200m
Sponsor: University of Dundee

Current Primary Outcome: 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 ]

Original Primary Outcome: The primary outcome is to determine 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 ]

Current Secondary Outcome:

  • 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.
  • 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 ]
  • 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 ]
  • 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 ]
  • To measure changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo. [ Time Frame: Following 1 year of therapy ]
  • 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 ]


Original Secondary Outcome:

  • 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.
  • To determine if there is a 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 ]
  • 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 ]
  • To determine if there is a 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 ]
  • To determine if there are changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo. [ Time Frame: Following 1 year of therapy ]
  • To assess, if there are 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 ]


Information By: University of Dundee

Dates:
Date Received: September 18, 2013
Date Started: September 2013
Date Completion:
Last Updated: November 3, 2016
Last Verified: November 2016