Type 2 Diabetes Mellitus
Conditions
Keywords
biscuit containing Salacia reticulate, randomised controlled trial
Brief summary
The investigators intend to conduct a triple blind randomized clinical trial to investigate the effect of a biscuit containing herbal extract, available in the market on the fasting blood sugar control in patients with diabetes mellitus and also to find out whether there are any side effects on other vital organs such as kidneys and liver.
Detailed description
The effect of a biscuit containing the extract of Salacia reticulata (Kothala Himbutu) on the reduction of blood glucose levels in patients with Type 2 Diabetes Mellitus. A single center randomized triple blind placebo controlled two period two sequence crossover clinical trial.
Interventions
DRUGKothala Himbutu Biscuit
Kothala Himbutu biscuit (containing Salacia reticulata extract) as a snack. This herb has been used by traditional physicians to control blood sugar.
DIETARY_SUPPLEMENTPlacebo Biscuit
Placebo biscuit without the herbal extract of Kothala Himbutu (Salacia reticulate)
Sponsors
Rajarata University, Sri Lanka
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Randomization code (A or B) was made using a computer and inserted in a sealed, serially numbered, opaque envelopes. Participants were given a serial number after run-in period. Assistant opened the envelope and assigned the patient to either biscuit A or B. The manufacturers held randomization code. Investigators, patients and those assessing the analysis were masked to the group outcome. Both Kothala Himbutu (KH) and placebo biscuits are identical in size, wrapped in same cover, and packed in identical boxes. The investigators tasted both biscuits and KH biscuits were slightly darker with the same taste. The study product is available in the market. Patients participating in the trial were asked about prior consumption of KH biscuits bought from the market (to exclude contamination). At the end of each period patients were asked whether they could assume the type of biscuit (KH biscuit or placebo) given to them and their preference for the type.
Intervention model description
Patients with diabetes were screened and Type I Diabetes was excluded. The minimum run-in period was eight weeks and if the variability of HbA1c is more than 20%, excluded, to exclude patients with fluctuating glycaemia. As this is a crossover trial some degree of stability of the glycemic control is necessary to prevent excessive variation of HbA1c interfering with the study outcome. Participants were randomized to receive the KH or placebo biscuit. Oral hypoglycemic was continued and adjusted. Participants consumed KH or placebo biscuit for a period of 3 months as mid-morning and afternoon snack. Subsequently in the washout period of 1 month the participants did not consumed any biscuits. After, crossing over they continued biscuits for another 3 months. HbA1c was done at recruitment, after run-in period, at 3 months and on completion of the study. When there was deterioration of the glycaemic control patient was prescribed insulin, and withdrawn from the study.
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Type 2 diabetes for minimum period of 6 months 2. Aged between 30 and 65 years 3. Stable glycaemic control over the preceding 2-3 months. They will be initially selected from a range of HBA1C varying from 6.5 - 14 and the individual subject should not have a variation of \>20% between the previous HBA1C and the HBA1C done at the commencement of the study
Exclusion criteria
1. Chronic kidney disease with estimated Glomerular filtration rate less than 30ml/hour 2. Severe valvular heart disease or heart failure. 3. Those on Insulin therapy 4. Severe liver disease (AST \> 10 X times the upper limit)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycosylated Haemoglobin | After 3 months and after 7 months (there is one month wash over period as this is a cross over trial) | HBA1c were analyzed at a centrally accredited lab using ion exchange high performance liquid chromatography standardized to NGSP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver Adverse Effects | Baseline, after 3 months, and after 7 months | liver functions are described in the table below with higher liver enzymes suggesting injury to the liver. |
| Renal Adverse Effects -1 | baseline, after 3 months and after 7 months | Renal functions are described in the table below with Lower estimated Glomerular Filtration Rate (eGFR) suggesting injury to the kidney. |
| Renal Adverse Effects - 2 | Baseline, after 3 months, and after 7 months | Renal functions are described in the table below with higher serum creatinine suggesting injury to the kidney. |
Countries
Sri Lanka
Participant flow
Recruitment details
All recruitment carried out in medical clinic, Teaching Hospital anuradhapura
Pre-assignment details
Run-in period was 8 weeks and if the variability of the HbA1c is more than 20%, participants were excluded. This was done to exclude patients with fluctuating glycaemia. Wash out for 1 month after 1st period of giving treatment for 3 months. After the wash out patients are crossed over for the other biscuit given for another three months
Participants by arm
| Arm | Count |
|---|---|
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group first given placebo biscuit for three months and after wash out period of one month given Kothala Himbutu biscuit (extract of Salacia reticulata) for three moths | 62 |
| Kothala Himbutu First Then Placebo Biscuit Group first given Kothala Himbutu biscuit (extract of Salacia reticulata) for three months and after wash out period of one month given placebo biscuit for three moths | 71 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Period of Three Months | Death | 1 | 0 |
| First Period of Three Months | Insulin Started | 1 | 1 |
| First Period of Three Months | Lost to Follow-up | 2 | 1 |
| Second Period of 3 Months | insulin started | 0 | 1 |
| Second Period of 3 Months | Lost to Follow-up | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Kothala Himbutu First Then Placebo Biscuit Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 71 Participants | 133 Participants |
| Age, Continuous | 50.3 years STANDARD_DEVIATION 8.4 | 50.7 years STANDARD_DEVIATION 7.1 | 50.5 years STANDARD_DEVIATION 7.7 |
| Glycosylated Haemoglobin | 8.45 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.4 | 8.65 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.44 | 8.56 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 62 Participants | 71 Participants | 133 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Sri Lanka | 62 participants | 71 participants | 133 participants |
| Sex: Female, Male Female | 42 Participants | 51 Participants | 93 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 131 | 0 / 129 |
| other Total, other adverse events | 0 / 131 | 0 / 129 |
| serious Total, serious adverse events | 1 / 131 | 0 / 129 |
Outcome results
Primary
Glycosylated Haemoglobin
HBA1c were analyzed at a centrally accredited lab using ion exchange high performance liquid chromatography standardized to NGSP
Time frame: After 3 months and after 7 months (there is one month wash over period as this is a cross over trial)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Glycosylated Haemoglobin | After period 1(3 months) | 8.36 percentage of glycosylated hemoglobin | Standard Error 0.19 |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Glycosylated Haemoglobin | After period 2 (trial end-7 months) | 8.23 percentage of glycosylated hemoglobin | Standard Error 0.21 |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Glycosylated Haemoglobin | After period 1(3 months) | 8.16 percentage of glycosylated hemoglobin | Standard Error 0.2 |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Glycosylated Haemoglobin | After period 2 (trial end-7 months) | 8.53 percentage of glycosylated hemoglobin | Standard Error 0.21 |
Secondary
Liver Adverse Effects
liver functions are described in the table below with higher liver enzymes suggesting injury to the liver.
Time frame: Baseline, after 3 months, and after 7 months
Population: adverse events analysis was only people who have completed or accessible for analysis. this was not a intention to treat analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | ALT (IU/L) after 3 months | 39 International Units per Liter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | AST (IU/L) at baseline | 28 International Units per Liter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | ALT (IU/L) at baseline | 38 International Units per Liter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | AST (IU/L) after 3 months | 28 International Units per Liter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | ALT (IU/L) after 7 months | 37 International Units per Liter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Liver Adverse Effects | AST (IU/L) after 7 months | 27 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | ALT (IU/L) after 7 months | 34 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | ALT (IU/L) at baseline | 37 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | ALT (IU/L) after 3 months | 36 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | AST (IU/L) after 7 months | 24 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | AST (IU/L) at baseline | 28 International Units per Liter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Liver Adverse Effects | AST (IU/L) after 3 months | 26 International Units per Liter |
Secondary
Renal Adverse Effects -1
Renal functions are described in the table below with Lower estimated Glomerular Filtration Rate (eGFR) suggesting injury to the kidney.
Time frame: baseline, after 3 months and after 7 months
Population: adverse events analysis was only people who have completed or accessible for analysis. this was not a intention to treat analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) at baseline | 77.1 milliliters/minute/1.73m^2 |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) after 3 months | 75.0 milliliters/minute/1.73m^2 |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) after 7 months | 75.0 milliliters/minute/1.73m^2 |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) at baseline | 76.0 milliliters/minute/1.73m^2 |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) after 3 months | 75.0 milliliters/minute/1.73m^2 |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects -1 | eGFR (ml/min/1.73m^2) after 7 months | 76 milliliters/minute/1.73m^2 |
Secondary
Renal Adverse Effects - 2
Renal functions are described in the table below with higher serum creatinine suggesting injury to the kidney.
Time frame: Baseline, after 3 months, and after 7 months
Population: adverse events analysis was only people who have completed or accessible for analysis. this was not a intention to treat analysis
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) at baseline | 0.94 milligrams per deciliter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) after 3 months | 0.98 milligrams per deciliter |
| Placebo Biscuit First Then Kothala Himbutu Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) after 7 months | 0.97 milligrams per deciliter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) at baseline | 0.94 milligrams per deciliter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) after 3 months | 0.96 milligrams per deciliter |
| Kothala Himbutu Biscuit First Then Placebo Biscuit Group | Renal Adverse Effects - 2 | Serum creatinine (mg/dL) after 7 months | 0.93 milligrams per deciliter |