Clinical trial NCT04931030: Low Carbohydrate Diet in Diabetic Kidney Disease
Official title: Effects of Low Carbohydrate Diet (LCBD) on Weight and Renal Outcome in Patients With Diabetic Kidney Disease (DKD)- A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Diabetic Kidney Disease
Obesity
Keywords: low carbohydrate diet
chronic kidney disease
diabetes mellitus
Lead sponsor: Universiti Teknologi Mara
Sponsor class: OTHER
Collaborators: name: International Medical University
First posted: 2021-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, unblinded, dietary intervention
Primary purpose: TREATMENT

Brief summary: The current population of type 2 diabetes mellitus (T2DM) worldwide is over 200 million and Malaysia contributes to 1.2% of that number. The prevalence of T2DM in Malaysia has approximately tripled over the last three decades from 6.3% in 1986 to 17.5% of the adult population in 2015.T2DM is a progressive disease associated with debilitating microvascular and macrovascular complications. The prevalence of chronic kidney disease (CKD) in Peninsular Malaysia was high at 9.1% of the adult population in 2011. T2DM is the leading cause of renal failure for patients commencing dialysis, increasing from 53% of new dialysis patients in 2004 to 61% in 2013. Therefore, diabetic kidney disease (DKD) is a debilitating complication which not only imposes significant health problems but also confers financial burden on affected patients. There has been increasing amount of understanding in the complexity of the relationship between T2DM and obesity. As the prevalence of both conditions continue to demonstrate a parallel rise, the influence of obesity on T2DM is further marked. Thus, this has led to greater emphasis on weight loss in the management of T2DM. More recent anti-diabetic medications including SGLT-2 inhibitors and GLP1 agonists demonstrated greater efficacy in improving glycaemic control and their ability to produce weight reduction. In addition, there has been more interest in the effects of these drugs on retardation of renal disease progression. The mechanism is unclear, either attributed by direct drug effects on renal glomerular-tubular structures, through the Renin-Angiotensin-Aldosterone-System (RAAS), or other pathways. Another pausible explanation is the significant weight loss, which has been shown to have a significant effect of attenuation of renal disease.

Weight reduction programs have long been a complex and tedious treatment plan which has inconsistent, non-duplicable and unpredictable outcomes. Most programs emphasized on medical nutrition therapy and lifestyle changes. There has been many different dietary plans which share a common goal ie to reduce calori intake whilst increasing energy expenditure. Few have been successfully reproducible, limited by either patient adherence or modest outcome.

Low carbohydrate diet is a diet plan which stresses on reducing carbohydrate intake to less than 20g daily. Numerous studies have shown that weight loss could be obtained by reduction of calori intake in either the form of carbohydrate or fat. CKD patients are recommended to consume low protein diet of less than 0.6-0.7g/kg/day with little emphasis on calori or carbohydrate intake.

This study, thus, aims to evaluate the effects of low carbohydrate and moderate fat (LCBD) in addition to low protein diet on renal disease in patients with DKD.

Detailed description: This is an investigator-initiated, single center, randomized, controlled, clinical trial in Type 2 diabetes mellitus patients, comparing 16-weeks of LCBD compared to standard medical therapy in patients with DKD.

Patients would be recruited from the Endocrinology and Nephrology clinics in UiTM Medical Specialist Center. Inclusion criteria would include patients aged between 40-75 years old, diagnosis with Type 2 DM of more than 5 years with stable CKD stage 2 and 3 of more than 6 months, HbA1c of 7% - 10.5%.

Exclusion Criteria include patients with Type 1 DM, experiencing frequent hypoglycaemia, abnormal liver function tests, heart failure (New York Heart Association functional class III-IV), active systemic inflammatory disease, chronic renal failure requiring hemodialysis, active hepatic disease and collagen disease, malignancy, recent hospital admission within the past 3 months, pregnant women, breastfeeding or planning to conceive within the next year.

Following informed consent, patients would be randomised to either LCBD or low protein Diet (LPD) group.

All recruited patients will be given the standard dietary and exercise advice which will include low protein of 0.6-0.7g/kg/day and low salt diet.

In addition, patients within the LCBD will be given a prescription diet of 20g of carbohydrate daily. This will be supplemented by visual aids on carbohydrate counts of various local food. Patients would be given the option to choose their most appropriate food types which will amount to the carbohydrate count given. Patients on oral anti-diabetic treatment including insulin will advised on titrations of their medications to avoid hypoglycaemia.

The control arm will not be given any additional advice. All patients will be required to fill in a 3-day food diary during their scheduled visits which will be at 8 weeks and 16 weeks.

Clinical assessments include blood sampling of approximately 8 ml which will be done at baseline and at study end.

Eligibility criteria: Inclusion Criteria

1. Diagnosed with Type 2 DM of more than 5 years
2. Diagnosis of stable CKD of more than 6 months
3. CKD stage 2 and 3
4. HbA1c of 7% - 10.5%
5. Patient age between 40-75 years old
6. Able to sign informed consent

Exclusion Criteria

1. Type 1 DM
2. Frequent hypoglycaemia
3. Persistent elevations of serum transminase
4. Heart failure (New York Heart Association functional class III-IV), active systemic inflammatory disease, chronic renal failure requiring hemodialysis, active hepatic disease and collagen disease
5. Malignancy
6. Recent hospital admission for acute within the past 3 months
7. Pregnant women, breastfeeding or planning to conceive within the next year

Primary outcomes:
measure: Change from baseline serum Creatinine at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline urine microalbuminuria at 12 weeks
timeFrame: Study end at 12 weeks
Secondary outcomes:
measure: Change from baseline HbA1c at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline fasting plasma glucose at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline lipid levels at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline weight at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline hip circumference (HC) at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline waist circumference (WC) at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline estimated visceral adispose tissue (Est VAT) at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline blood pressure at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline highly sensitivity C-reactive protein (hsCRP) at 12 weeks
timeFrame: Study end at 12 weeks
measure: Change from baseline Interleukin-6 (IL-6) at 12 weeks
timeFrame: Study end at 12 weeks
Other outcomes:
Locations:
city: Petaling Jaya
country: Malaysia
facility: Universiti Teknologi MARA
state: Selangor
Study officials:
References:
citation: Feisul MI, Azmi S. (Eds). National Diabetes Registry Report, Volume 1, 2009-2012. Kuala Lumpur; Ministry of Health Malaysia; 2013 Jul.
citation: National Health and Morbidity Survey 2015 (NHMS 2015). Ministry of Health, Kuala Lumpur, Malaysia
citation: Hooi LS, Ong LM, Ahmad G, Bavanandan S, Ahmad NA, Naidu BM, Mohamud WN, Yusoff MF. A population-based study measuring the prevalence of chronic kidney disease among adults in West Malaysia. Kidney Int. 2013 Nov;84(5):1034-40. doi: 10.1038/ki.2013.220. Epub 2013 Jun 12.
citation: B. Goh, L. Ong, Y. Lim. Twenty First Report of the Malaysian Dialysis and Transplant 2013. Malaysian Society of Nephrology, Kuala Lumpur, Malaysia (2014)