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

NCT01951404 | Completed Phase 4 DMC

• 1 other identifier: 2012CV07
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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.

Conditions

End Stage Renal Disease; Left Ventricular Hypertrophy

Keywords

Left Ventricular Hypertrophy; Allopurinol; End Stage Renal Disease; Haemodialysis; Renal Replacement Therapy; MRI

Outcome Measures

Primary Outcomes (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.

  following 1 year of therapy

Secondary Outcomes (6)

• To decide on optimum dosing regime of allopurinol in End Stage Renal Disease from pilot study

  6 weeks

• To measure any difference in endothelial function with allopurinol compared with placebo, measured by Flow Mediated Dilatation and Pulse Wave Analysis

  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

  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.

  Following 1 year of therapy

• To measure changes in inflammatory blood markers, in ESRD with allopurinol compared with placebo.

  Following 1 year of therapy

Study Arms (2)

Allopurinol

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

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)

Interventions

Allopurinol DRUG

Allopurinol

Placebo (for allopurinol) DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Dundee: lead
• British Heart Foundation: collaborator
• NHS Tayside: collaborator
• NHS Greater Glasgow and Clyde: collaborator
• University of Glasgow: collaborator

Study Sites (3)

NHS Greater Glasgow and Clyde

Glasgow, La, G12 8TA, United Kingdom

Location

NHS Tayside

Dundee, Tayside, DD9 1SY, United Kingdom

Location

NHS Ayrshire and Arran

Crosshouse, KA2OBE, United Kingdom

Location

Related Publications (1)

• Kao MP, Ang DS, Gandy SJ, Nadir MA, Houston JG, Lang CC, Struthers AD. Allopurinol benefits left ventricular mass and endothelial dysfunction in chronic kidney disease. J Am Soc Nephrol. 2011 Jul;22(7):1382-9. doi: 10.1681/ASN.2010111185. Epub 2011 Jun 30.

  PMID: 21719783 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Hypertrophy, Left Ventricular

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Allan D Struthers, BSc, MD, FRCP, FESC, FRSE

  Centre for Cadiovascular Medicine, University of Dundee

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Fellow - Principal Investigator

Study Record Dates

• First Submitted: September 18, 2013
• First Posted: September 26, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: November 4, 2016

Record last verified: 2016-11

Locations

GB (3)