The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12614001171606
Ethics application status
Approved
Date submitted
21/10/2014
Date registered
7/11/2014
Date last updated
7/11/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Transplantation and Diabetes (Transdiab): A Pilot Randomised Controlled Trial of Metformin in pre-diabetes after kidney transplantation
Scientific title
To evaluate the feasibility, safety and tolerability of metformin in pre-diabetic kidney transplant patients
Secondary ID [1] 285526 0
Nil known
Universal Trial Number (UTN)
U1111-1159-7169
Trial acronym
TRANSDIAB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
New onset diabetes after kidney transplantaton 293341 0
Condition category
Condition code
Renal and Urogenital 293607 293607 0 0
Kidney disease
Metabolic and Endocrine 293608 293608 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral Glucose Tolerance Test in all consenting renal transplant patients
Randomisation of all with IGT to metformin or standard care

Intervention Metformin 500mg twice daily orally for 12 months plus standard care.

Standard care is dietary advise with a dietician and advise about exercise three times weekly

Adherence monitored by medication return
Intervention code [1] 290468 0
Prevention
Comparator / control treatment
Standard advise on diet and exercise: this is with a dietician review at one month post transplantation giving advice about a healthy diet and regular exercise 3 x weekly.
Control group
Active

Outcomes
Primary outcome [1] 293416 0
Feasibility of Recruitment - all patients in transplant clinic will be approached. Therefore feasibility will be examined by examining consent rate.
Timepoint [1] 293416 0
12 months after recruitment
Primary outcome [2] 293417 0
Tolerability of Metformin: using Gastrointestinal Symptom Rating Scale (GSRS)
Timepoint [2] 293417 0
baseline, month 3, month 12 after transplant
Primary outcome [3] 293418 0
Efficacy of metformin - glucose, HbA1c
Timepoint [3] 293418 0
3,6,9,12 months post transplant
Secondary outcome [1] 310986 0
Discontinuation of metformin due to adverse events as assessed yes or no.
Any reason for discontinuation will be recorded as Adverse event. It is anticipated most discontinuations will be for side effects.
Timepoint [1] 310986 0
12 Months post transplant
Secondary outcome [2] 310987 0
weight change using digital weighing scales
Timepoint [2] 310987 0
12 months post transplant
Secondary outcome [3] 310989 0
All adverse events - ie any events patient reports including reasons for all new medications. Will be assessed by primary investigator
Timepoint [3] 310989 0
12 months post transplant
Secondary outcome [4] 310990 0
Major Adverse Cardiac Events using discharge summaries
Timepoint [4] 310990 0
12 months post transplant - all discharge summaries from the first year will be reviewed at 12 monhts post transplantation.
Secondary outcome [5] 310991 0
Proportion of patients who revert to normal glucose metabolism after oral glucose tolerance test
(OGTT)
Timepoint [5] 310991 0
12 months post transplant

Eligibility
Key inclusion criteria
Renal Transplant
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pre-existing diabetes before transplant

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
all patients will be approached in renal transplant clinic
Treatment allocation not blinded

Allocation concealment using sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using cards in envelopes with a table created by comupterised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The recruitment rate will be determined by the ratio of the number of patients screened with an OGTT to the number of randomised patients. The differences in the binary outcome measures between the groups will be assessed by the Fisher’s exact test or the Chi-square test as appropriate. The treatment effect on the continuous outcome measures (FPG, HbA1c, weight, lipid profile) will be assessed by using analysis of covariance (ANCOVA), adjusting for baseline values, or linear mixed models. If data are not normally distributed, data transformation will be performed. The time to requirement of additional therapy (i.e. commencement of insulin) will be analysed by Kaplan-Meier analysis. Risk factors for the requirement of additional therapy will be analysed using Logistic regression models.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6427 0
New Zealand
State/province [1] 6427 0
Auckland

Funding & Sponsors
Funding source category [1] 290125 0
Charities/Societies/Foundations
Name [1] 290125 0
A+ Trust
Address [1] 290125 0
Auckland City Hospital, 2 Park Road, Grafton
Auckland 1142
Country [1] 290125 0
New Zealand
Primary sponsor type
Government body
Name
Auckland District Health Board
Address
Auckland City Hospital, 2 Park Road, Grafton, Auckland,1142 NZ
Country
New Zealand
Secondary sponsor category [1] 288840 0
None
Name [1] 288840 0
Address [1] 288840 0
Country [1] 288840 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291836 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 291836 0
C/o MEDSAFE, Level 6
10 Brandon Street
Wellington
6011
Ethics committee country [1] 291836 0
New Zealand
Date submitted for ethics approval [1] 291836 0
Approval date [1] 291836 0
03/10/2014
Ethics approval number [1] 291836 0
14/STH/129

Summary
Brief summary
Diabetes occurs in up to 50% of patients after kidney transplantation and is associated with increased mortality and transplant failure. We propose a pilot randomised controlled trial of Metformin compared with standard of care in patients who develop impaired glucose tolerance or elevated fasting plasma glucose early after kidney transplantation aiming to determine safety and tolerability of Metformin, the incidence of development of diabetes, and the effect of Metformin on body weight at 12 months after transplantation.

All consenting patients transplanted at Auckland City Hospital who do not have pre-existing diabetes will be enrolled in the study. Patients will undergo an oral glucose tolerance test when clinically stable at 4 – 6 weeks after kidney transplantation. Patients who have an elevated fasting glucose, or impaired glucose tolerance will be randomised to Metformin in addition to standard of care advice regarding diet and exercise, or standard advice alone. Follow up will be for 12 months.

Metformin has been shown to prevent development of diabetes in the general population. Additionally it does not cause hypoglycaemia and has beneficial effects on all cause and cardiac mortality. Demonstration that Metformin is well tolerated in the group at highest risk of developing diabetes and assessment of its effect on serum glucose will advise on numbers required to investigate the effect of this drug in preventing diabetes in a larger study. As outcomes of all consenting patients will be followed, information regarding the incidence of diabetes and glucose intolerance in our population over a year will also be generated.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52218 0
A/Prof Helen Pilmore
Address 52218 0
Department of Renal Medicine, Auckland City Hospital, 2 Park Road, Grafton, 1142, Auckland
Country 52218 0
New Zealand
Phone 52218 0
+64 9 379 7440
Fax 52218 0
+64 9 307 4987
Email 52218 0
hpilmore@adhb.govt.nz
Contact person for public queries
Name 52219 0
A/Prof Helen Pilmore
Address 52219 0
Department of Renal Medicine, Auckland City Hospital, 2 Park Road, Grafton, 1142, Auckland
Country 52219 0
New Zealand
Phone 52219 0
+64 9 379 7440
Fax 52219 0
+64 9 307 4987
Email 52219 0
hpilmore@adhb.govt.nz
Contact person for scientific queries
Name 52220 0
A/Prof Helen Pilmore
Address 52220 0
Department of Renal Medicine, Auckland City Hospital, 2 Park Road, Grafton, 1142, Auckland
Country 52220 0
New Zealand
Phone 52220 0
+64 9 379 7440
Fax 52220 0
Email 52220 0
hpilmore@adhb.govt.nz

No information has been provided regarding IPD availability
Summary results
No Results