Clinical trial NCT04917458: Cholecalciferol on Depressive Symptoms in Type 2 Diabetes Mellitus Patients
Official title: Effects of Cholecalciferol on Depressive Symptoms in Type 2 Diabetes Mellitus Patients: Study of Neurotrophin-3, Serotonin, and C-Peptide
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Depressive Symptoms
Keywords: Diabetes Mellitus, Type 2
Depression
Cholecalciferol
Lead sponsor: Indonesia University
Sponsor class: OTHER
First posted: 2021-06-08
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This is a prospective, randomized, double blind, and controlled clinical study to investigate the effects of cholecalciferol on depressive symptoms in type 2 diabetes mellitus patients. Patients included into the study will be randomized into two groups and receive placebo (as control group) or cholecalciferol administered orally for 3 months.
Primary purpose: TREATMENT

Brief summary: One in eleven adults falls ill with Diabetes Mellitus (DM) and 90% of them suffered from type 2 DM. Depression in type 2 DM patients had a big impact, acting as a major barrier to self-care in type 2 DM patients. Depression in diabetes patients is also associated with decreasing quality of life. Poor self-care behavior and adherence, poor glycemic control, and increased risk of mortality about 36-38% from cardiovascular complications are other known debilitating results.

Vitamin D receptors are present in many organ systems, namely the pancreas, intestine, musculoskeletal, and nervous systems. Vitamin D has pleiotropic effects, which were seen from its mechanism as an anti-inflammatory, anti-apoptotic, and immunomodulatory agent. Based on the mechanism of Vitamin D action in the nervous system, which also plays a role in depression pathogenesis, vitamin D is hypothesized to have a beneficial effect on depression, both for depression prevention and treatment. Few studies denote that Vitamin D can improve depression in type 2 DM patients. Vitamin D may become an important adjuvant therapy to ameliorate depression in type 2 DM patients. These clinical trials concerning vitamin D in type 2 DM are relevant, reminding that type 2 DM resulted in higher morbidity, mortality, and numerous high-risk complications in the population.

Detailed description: According to World Health Organization report's, depression was estimated causing distress in most people on 2030. 1 In Indonesia, the prevalence of depression in 2017 was 3,7%.2 Depression often found in Internal medicine patient's as a comorbid in various chronic diseases. 3 One of the most common chronic disease is type 2 diabetes mellitus. There's one in eleven adults suffered from diabetes mellitus, and 90% of them had type 2 diabetes mellitus (DM). Basic Health Research Data on 2018 showed there were 10.9% case type 2 DM in Indonesia. 4 DKI Jakarta Province had 3,4% or 11.226 people aged 15 years and over with Diabetes Mellitus and had been a highest prevalence of Diabetes Mellitus among population aged 15 years and over. Meanwhile, prevalence of depression among adults aged 15 and over in DKI Jakarta was 5.9%. Seminkovics K et al5 reported one in four people with type 2 diabetes mellitus suffered from depression in United States. In Indonesia, Nasrun WMS6 reported there were 27,6% prevalence of depression in type 2 diabetes mellitus patients's with cognitive impairment, while Arshita et al7 found there were 60% patients with depression in type 2 diabetes mellitus patients with pedic ulcers in RSCM .

Depression in type 2 Diabetes Mellitus patients had a big impact, such as: depression can be a major barrier to self-care in type 2 diabetes mellitus patients. 1,5 Depression in diabetes patients is also associated with decreasing quality of life. 6 Poor of self-care behavior and adherence, poor of glycemic control, and increased risk of mortality about 36-38% from cardiovascular complication are other known debilitating results. 8 Vitamin D receptors are present in various organs such as the pancreas, intestine, musculoskeletal, and nervous system. Vitamin D has a pleiotrophic effect which were seen from its mechanism as anti-inflammatory, anti-apoptotic, and immunomodulatory. 16 Based on mechanism of Vitamin D action in nervous system, which also plays a role in the depression pathogenesis, vitamin D is hypothesized to have a beneficial effect on depression, both for prevention and treat the pathomechanism. The protective effect of Vitamin D for prevent depression had been widely studied in copious observational epidemiological studies, although with diversified results. Many studies have been conducted to assess the beneficial effects of vitamin D on a variety outcomes including depression, which are summarized in systematic reviews and meta-analyzes of observational studies. A meta-analyses by Ju SY et al38 found that low plasma 25 (OH) D levels were associated with and increased risk of depression in a cross sectional study with 43,1377 participants.

Vitamin D deficiency is a worldwide health problem. Vitamin D had known as an important role in biological processes, calcium homeostasis, and various health problems. In addition to its role in musculoskeletal, vitamin D is also associated with a few non-musculoskeletal diseases such as immunity, cancer, cardiovascular disease, hypertension, diabetes, and psychological problems like dementia or depression. 17 Both Vitamin D and its analogues are natural ligands for vitamin D receptor (VDR). Vitamin D receptors are widely distributed throughout body including brain and pancreas. Vitamin D receptors found in cerebellum, hippocampus, substantia nigra, basal forebrain, prefrontal cortex and hypothalamus. This explains the role of vitamin D in brain development and emotional disorders. In brain development, vitamin D played role in proliferation and differentiation of neuron cells. In adult brain, vitamin D played a role in neurogenesis in the hippocampus and synthesizes neurotransmitters such as dopamine, GABA, and serotonin. 18 It's known as depression neurotransmitter.

Other studies showed that vitamin D might repair neurotransmitters, inflammation, metabolic, and oxidative stress. Cholecalciferol will activate 1-α hydroxylase enzymes and P450 cytochrome, which transformed calcifediol hydroxylation into activated vitamin D in central nervous system, so that improving depression. Anti depressants such as SSRIs (Selective serotonin reuptake inhibitors), can induce gastrointestinal bleeding in patients whose taking anti-platelets or anti-coagulants, increase weight and dyslipidemia. Thus, other studies therapy based on pathogenesis of depression, effective and side effects need to be done.

Few studies denote that Vitamin D can improve depression in type 2 DM patients. Those studies used only Beck Depression Inventory test to assess depression without any biological markers. Vitamin D may become an important adjuvant therapy to ameliorate depression in type 2 DM. These clinical trials concerning vitamin D in type 2 DM are relevant, reminding that type 2 DM resulted in higher morbidity, mortality and numerous high risk complication in the population.

Methods/Design: This is a prospective, randomized, double blind, and controlled clinical study to investigate the effects of cholecalciferol on depressive symptoms in type 2 diabetes mellitus patients. Patients included into the study will be randomized into two groups and receive placebo (as control group) or cholecalciferol administered orally for 3 months.

Discussion : Vitamin D may become an important adjuvant therapy to ameliorate depression in type 2 DM patients. Thus, type 2 diabetes mellitus with depression symptoms will have a better quality of life.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects with aged 18 and over
* Living in around Jakarta
* Type 2 diabetes mellitus patients with depression symptom
* Patients with Body mass index 20-30 m/kg2
* Patients are able and willing to maintain diet, physical activity, and lifestyle for 3 months
* Patients are able and willing to control for follow up

Exclusion Criteria:

* - Presence of severe hepatic dysfunction, defined as cirrhosis hepatic
* Presence of severe renal dysfunction, defined as chronic kidney disease stage 5 or e-GFR ≤15 or history of hemodialysis
* Patients with acute coronary syndrome
* Presence of acute systemic inflammatory response syndrome (SIRS). The term SIRS describes a clinical state arising from a non-specific cause, infective, or otherwise
* Recent obtained vitamin D therapy within the last 3 months
* Current or regular use of corticosteroids within immunosuppressant dosage
* Presence of major depression
* Presence of psychosis
* Current or regular use of anti-depressant
* Current or regular use of phenytoin or phenobarbital
* For females: current pregnancy and lactation period
* Patients who refuse the studies

Primary outcomes:
measure: Evaluating the effects of cholecalciferol for depression symptoms with BDI II score
timeFrame: 90 days
Secondary outcomes:
measure: Evaluating the effects of cholecalciferol against neuroplasticity (NT-3)
timeFrame: 30 days
measure: Evaluating the effects of cholecalciferol against serotonin
timeFrame: 30 days
measure: Evaluating the effects of cholecalciferol against C-Peptide
timeFrame: 30 days
Other outcomes:
Locations:
city: Jakarta Pusat
country: Indonesia
facility: Cipto Mangunkusumo National General Hospital
state: DKI Jakarta
Study officials:
affiliation: Indonesia University
name: Rudi Putranto
role: PRINCIPAL_INVESTIGATOR
References: