Intervention Review

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Lifestyle interventions for chronic gout

  1. John HY Moi1,*,
  2. Melonie K Sriranganathan2,
  3. Christopher J Edwards2,
  4. Rachelle Buchbinder3

Editorial Group: Cochrane Musculoskeletal Group

Published Online: 31 MAY 2013

DOI: 10.1002/14651858.CD010039.pub2


How to Cite

Moi JHY, Sriranganathan MK, Edwards CJ, Buchbinder R. Lifestyle interventions for chronic gout. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD010039. DOI: 10.1002/14651858.CD010039.pub2.

Author Information

  1. 1

    The Royal Melbourne Hospital, Department of Rheumatology, Parkville, Victoria, Australia

  2. 2

    University Hospital Southampton NHS Foundation Trust, Department of Rheumatology, Southampton, Hampshire, UK

  3. 3

    Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Monash Department of Clinical Epidemiology, Cabrini Hospital, Malvern, Victoria, Australia

*John HY Moi, Department of Rheumatology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria, 3050, Australia. john.moi@mh.org.au.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 31 MAY 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]

MethodsRandomised, double blind, 3-arm, parallel-group, controlled trial

Duration: 3 months

Withdrawals: 18 (distribution of losses not known despite attempts to contact the study author)

Pre-specified sample size calculation: reported

Intention-to-treat analysis: performed


ParticipantsN = 120

Inclusion criteria:

1. Adults aged ≥ 18 years

2. Gout diagnosed (according to the American College of Rheumatology diagnostic classification, recurrent gout flares (at least 2 flares in the preceding 4 months)

3. Participants experiencing frequent gout flares at the time of study enrolment (≥ 2 flares in the preceding 4 months)

Exclusion criteria:

1. Lactose intolerance
2. Severe renal impairment (defined as estimated glomerular filtration rate (eGFR) < 30 ml/min)

Lactose group (n = 40):

1. Males, n (%): 37 (93)

2. Mean age, years (SD): 57 (16)

3. Caucasian ethnicity, n (%): 28 (70)

4. Number of self reported flares in preceding 4 months, mean (SD): 3.9 (2.7)

5. Number of gout flares in baseline month, mean (SD): 1.3 (1.5)

6. Allopurinol use, n (%): 21 (53)

7. Colchicine use, n (%): 12 (30)

8. Prednisone use, n (%): 4 (10)

9. NSAID use, n (%): 11 (28)

10. Diuretic use, n (%): 2 (5)

11. Serum urate, mmol/l, mean (SD): 0.44 (0.11)
12. Tophaceous gout, n (%): 8 (20%)

13. Serum creatinine, μmol/l, mean (SD): 91 (18)

SMP group (n = 40):

1. Males, n (%): 36 (90)

2. Mean age, years (SD): 56 (12)

3. Caucasian ethnicity, n (%): 28 (70)

4. Number of self reported flares in preceding 4 months, mean (SD): 4.5 (2.3)

5. Number of gout flares in baseline month, mean (SD): 1.1 (1.4)

6. Allopurinol use, n (%): 22 (55)

7. Colchicine use, n (%): 7 (18)

8. Prednisone use, n (%): 8 (20)

9. NSAID use, n (%): 10 (25)

10. Diuretic use, n (%): 1 (2.5)

11. Serum urate, mmol/l, mean (SD): 0.41 (0.09)
12. Tophaceous gout, n (%): 17 (43)

13. Serum creatinine, μmol/l, mean (SD): 91 (19)

SMP/GMP/G600 (n = 40):

1. Males, n (%): 35 (88)

2. Mean age, years (SD): 56 (13)

3. Caucasian ethnicity, n (%): 22 (55)

4. Number of self reported flares in preceding 4 months, mean (SD): 5.1 (9.6)

5. Number of gout flares in baseline month, mean (SD): 1.8 (2.4)

6. Allopurinol use, n (%): 22 (55)

7. Colchicine use, n (%): 13 (33)
8. Prednisone use, n (%): 4 (10)
9. NSAID use, n (%): 11 (28)
10. Diuretic use, n (%): 8 (20)

11. Serum urate, mmol/l, mean (SD): 0.42 (0.11)
12. Tophaceous gout, n (%): 10 (25)

13. Serum creatinine, μmol/l, mean (SD): 93 (20)


InterventionsIntervention 1: lactose powder active control

Intervention 2: skim milk powder (SMP) active control

Intervention 3: SMP enriched with GMP and G600 (1.5 g GMP protein (10% total protein) and 0.525 g G600 (3.5% of total protein weight))


OutcomesOutcome assessments at 1, 2 and 3 months:

Primary endpoint: change in frequency of gout flares

Secondary endpoints:

1. Change in swollen joint count (/66)

2. Change in tender joint count (/68)

3. Pain (10-point Likert), (scored 0 to 10) where 0 (no pain) and 10 (severe pain)

4. Patient global assessment (0 to 100), where 0 (very well) and 100 (very poor)

5. C-reactive protein (CRP) (mg/l)

6. Serum uric acid concentration (mmol/l)

7. Fractional excretion of UA (%)

8. Health Assessment Questionnaire (HAQ-II), 10-item questionnaire, each item scored from 0 (without any difficulty) to 3 (unable to perform). Sum of the scores of each questionnaire item is divided by the number of questions answered to obtain a value between 0 (minimal loss of function) and 3 (completely disabled)

9. Open-ended enquiry to elicit adverse events


NotesUnpublished data (HAQ results) sought and received from the study author


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomized using a random block randomization algorithm"

Allocation concealment (selection bias)Unclear riskQuote: "Participants and study staff were blinded to treatment allocation throughout the study..." Comment: insufficient details provided of the actual method of allocation concealment to intervention. No further information obtained in spite of attempts to contact the study author.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: "The products were dry-blended and packed into identical, custom-made aluminium foil sachets...Each intervention was a cream-coloured powder administered daily as a 250 ml vanilla flavoured shake"

Blinding of outcome assessment (detection bias)
Patient assessed outcomes
Low risk1. Gout flare frequency

2. Patient global assessment

3. Health assessment questionnaire (HAQ-II)

Blinding of outcome assessment (detection bias)
Examiner assessed outcomes
Unclear risk1. Tender joint count

2. Swollen joint count

3. Adverse events

Quote: "Study staff were blinded to treatment allocation throughout the study..." Comment: although not explicitly stated, it was implied from the aforementioned statement that outcome assessors were blinded. No further clarification was available despite attempts to contact the study author.

Blinding of outcome assessment (detection bias)
Laboratory assessed outcomes
Unclear risk1. Serum urate concentration

2. Fractional excretion of uric acid

3. C-reactive protein

Quote: "Study staff were blinded to treatment allocation throughout the study..." Comment: although not explicitly stated, it was implied from the aforementioned statement that outcome assessors were blinded. No further clarification was available despite attempts to contact the study author.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "Of the 120 patients enrolled in the study, two patients discontinued due to adverse events, eight were lost to follow-up, and eight continued in the study without taking the milk products after experiencing an adverse event (intention to treat). One hundred and two patients completed the study as per protocol." Comment: distribution of drop-outs between groups not specified. No further clarification was available despite attempts to contact the study author.

Selective reporting (reporting bias)Unclear riskComment: all prespecified outcomes reported. There was selective reporting of a post hoc comparison between SMP/GMP/G600 and lactose powder control on change in gout flare frequency and lowering of diastolic BP.

Other biasUnclear riskQuote: "The study was registered as a clinical trial with the Australian New Zealand Clinical Trials Registry (ACTRN12609000479202)". COI: "This work was funded by LactoPharma (a joint venture between Fonterra Ltd, Fonterra R&D Ltd and Auckland UniServices Ltd) and the New Zealand Government Foundation for Research Science and Technology. Barbara Kuhn-Sherlock, Alastair MacGibbon and Kate Palmano are employees of Fonterra Co-operative Group Ltd. Alastair MacGibbon, Nicola Dalbeth and Kate Palmano are named inventors on a patent application related to milk products and gout."

 
Characteristics of studies awaiting assessment [ordered by study ID]

Methods

Participants

Interventions

Outcomes

NotesAwaiting translation


Methods

Participants

Interventions

Outcomes

NotesAwaiting translation

 
Comparison 1. SMP (GMP/G600) versus control (SMP/lactose)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Number of gout flares per month, after 3 months SMP (GMP/G600) versus control (SMP/lactose)1Mean Difference (IV, Random, 95% CI)Subtotals only

 2 Physical Function1Mean Difference (IV, Random, 95% CI)Subtotals only

 3 Participant withdrawals due to adverse events1Risk Ratio (M-H, Random, 95% CI)Subtotals only

 
Summary of findings for the main comparison. Skim milk enriched with GMP/G600 compared to skim milk & lactose powder for chronic gout

Skim milk enriched with GMP/G600 compared to skim milk & lactose powder for chronic gout

Patient or population: patients with chronic gout
Settings: outpatient, community
Intervention: Skim milk enriched with GMP/G600
Comparison: skim milk & lactose powder

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Skim milk & lactose powderSkim milk enriched with GMP/G600

Acute gout attack frequency
participant self-report using gout flare diary
Follow-up: 3 months
The mean acute gout attack frequency in the control groups was
0.6997 Number of gout flares per month
The mean acute gout attack frequency in the intervention groups was
0.21 lower
(0.76 lower to 0.34 higher)
120
(1 study)
⊕⊕⊝⊝
low1
Not statistically significant2

Participant withdrawals due to adverse events
participant and study investigator reported
Follow-up: 3 months
Study populationRR 1.27
(0.53 to 3.03)
120
(1 study)
⊕⊕⊝⊝
low1
Not statistically significant3

138 per 1000175 per 1000
(73 to 417)

Moderate


Joint pain reduction
10-point Likert scale (0 is no pain)
Follow-up: 3 months
The mean joint pain reduction in the control groups was
-0.942
The mean joint pain reduction in the intervention groups was
1.03 lower
(1.96 to 0.1 lower)
120
(1 study)
⊕⊕⊝⊝
low1
Absolute risk difference = -10% (-20% to -1%). Relative percentage change = -39% (-74% to -4%). NNTB = 10 (5 to 100)2

Tophus regression - not measuredSee commentSee commentNot estimable-See commentNot measured

Physical function
HAQ-II. Scale from: 0 to 3; 0 is minimal loss of function.
Follow-up: 3 months
The mean physical function in the control groups was
0.11
The mean physical function in the intervention groups was
0.03 lower
(0.14 lower to 0.08 higher)
120
(1 study)
⊕⊕⊝⊝
low1
Absolute risk difference = -1% (-5% to 3%). Relative percentage change = -13% (-58% to 33%)

NNT n/a, not statistically significant2

Serum urate normalisation4 - not reportedSee commentSee commentNot estimable4-See commentNot reported

Serious adverse events
participant and study investigator reported
Follow-up: 3 months
38 per 100050 per 1000
(9 to 287)
RR 1.33
(0.23 to 7.66)
120
(1 study)
⊕⊕⊝⊝
low1
Gastrointestinal AEs (diarrhoea, nausea and flatulence) reported most commonly. SAE related to hospital admissions - none were due to the study products.3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 There was selective reporting of post-hoc comparisons between skim milk powder enriched with GMP/G600 and one of the two study controls (lactose) in relation to change in gout attack frequency from baseline
2 Number needed to benefit (NNTB) = N/A when result is not statistically significant. NNT for continuous outcomes calculated using the Wells calculator software available from the CMSG editorial office.
3 Number needed to harm (NNTH) = N/A when result is not statistically significant. NNT for dichotomous outcomes calculated using Cates NNT calculator (http://nntonline.net/ebm/visualrx/try.asp).
4 Results only presented graphically