Effect of Vitamin D Supplementation on Allostatic Load and Chronic Stress Along Line of Control in Azad Jammu Kashmir

Effect of Vitamin D Supplementation on the Allostatic Load and Chronic Stress Along Line of Control in Azad Jammu and Kashmir. "Double Blind Randomized Placebo-controlled Trial"

FULL TITLE Effect of vitamin D supplementation on the Allostatic load and Chronic stress along line of control in Azad Jammu and Kashmir. "Double blind randomized placebo-controlled trial"

SHORT TITLE Effect of vitamin D supplementation on allostatic load and chronic stress along line of control in azad Jammu and Kashmir PROTOCOL/VERSION DATE 5th August 2023 METHODOLOGY "Double blind randomized placebo-controlled trial"

STUDY DURATION 1 year STUDY CENTRES 1. District head quarter hospital haveli district Azad Kashmir 2. Rural health center (RHC) Khursheed Abad, 3. Basic health unit (BHU) Kirni Mandhaar and 4. First aid post (FAP) Chirikot. Main Objectives -To determine whether high-dose oral vitamin D supplementation effects allostatic load and chronic stress of the residents of line of control haveli district Azad Jammu and Kashmir (primary outcome)

• To assess the prevalence and determinants of allostatic load and chronic stress among the residents of line of control (secondary outcome factors analysis).
• To look into the relationship between chronic stress and vital clinical markers as blood pressure, BMI, and lipid profile in participants from line of control.
• To determine whether this intervention is safe and well-tolerated by study participants (secondary outcomes, safety) No. of Participants 120 Statistical Methodology and Analysis The collected data will be analysed using appropriate statistical techniques: Descriptive statistics will summarize participant characteristics, chronic stress, psychological well-being, physical health indicators, and baseline vitamin D levels. Inferential statistics, such as t-tests, ANOVA, and regression analysis, will be used to examine relationships between chronic stress, allostatic load, vitamin D supplementation, and health outcomes. Subgroup analyses will explore potential interactions based on demographic variables

Study Overview

• Status: Not yet recruiting
• Conditions: Mental Health Issue
• Intervention / Treatment: Dietary supplement: 25 hydroxy cholecalciferol (Vitamin D) /25(OH)D3.; Dietary supplement: Placebo

Detailed Description

The aim of this research is to fully comprehend the complex relationship between chronic stress, physiological dysregulation (as measured by allostatic load), and the potential impact of vitamin D supplementation on psychological well-being and physical health in a conflict-affected population.TRIAL ENDPOINTS Primary endpoint The primary outcome will be the Allostatic load after the 3 supplementation doses of study medication.

Secondary Efficacy Endpoints Serum concentration of vitamin D, HbA1C, lipid profile (HDL and LDL), serum cortisol and C reactive proteins after 4 months.

Any change in the Biophysical parameters (blood pressure (BP), heart rate (HR), body mass index (BMI) and hip waist ratio (HRR) after 4 months Chronic stress reduction after 4 months (dose effect) and determinants identification by sub group analysis.

Residents of warzone areas, such as District Haveli in Azad Kashmir, endure persistent exposure to chronic stressors resulting from conflict-related violence, displacement, and traumatic events. This chronic stress not only takes a toll on their mental health but also triggers physiological dysregulation across multiple systems, contributing to an increased allostatic load. Furthermore, the prevalent deficiency of vitamin D, exacerbated by limited sunlight exposure and disrupted food supplies, poses additional health risks in this population. Despite these challenges, there is a notable lack of comprehensive research investigating the determinants of allostatic load in the context of chronic stress and the potential ameliorative effects of vitamin D supplementation. Addressing this gap is crucial for understanding the intricate interplay between stress, physiological health, and potential interventions, thereby contributing to the well-being and resilience of residents in conflict-affected regions.STUDY DESIGN/STUDY PLACE:

The study will employ a It will be a double blinded, parallel individually randomized control trial and will be conducted in District Haveli, Azad Kashmir, armed conflicted area affected by conflict-related stressors.

STUDY POPULATION:

The study will include adult male/female) age (18-60 years) residents of District Haveli, Azad Kashmir, who have been exposed to war-related stressors, violence, and displacement.

SAMPLE SIZE Assuming that 60% of the participants in the control group arm would attain >30% of the baseline vitamin D status at 6 months, we calculated that a total of 94 participants (47 per arm) would need to complete follow-up in order to detect a 25% absolute increase (to 85%) in the proportion of patients attaining >30% vitamin D level at 6 months in the intervention arm with 80% power at the5% significance level(Giacomet et al., 2014). This number will be inflated to a total of 114 allow attrition due to death and loss to follow up. There will be interim analysis in the plan.

SAMPLING TECHNIQUE: The multi-stage cluster sample strategy is ideal for research done in places with geographical dispersion, limited access, and community-specific characteristics. STUDY TOOL:

The study will utilize a combination of validated questionnaires and physiological measurements to collect data.

DATA COLLECTION PROCESS; To reduce the burden of data collectors and make data collection process easier and accessible, data will be collected on google forms/kobo tool. Data collector team will be equipped with android mobile/tab, where kobo tool will be installed. Data will be gathered in offline mode as some of the bordering area, may not have access to internet, once team is back from field will synchronized the data in online mode. This way we will have complete data set at the same time to check quality and completeness, and remove errors through virtual backstopping.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: jawwad Af kayani, PhD; Phone Number: +923129117945; Email: drjawwadkayani@hsa.edu.pk

Study Locations

• Pakistan
  • Azad Jammu And Kashmir
    • Haveli, Azad Jammu And Kashmir, Pakistan, 12201
      • District Headquarter Hospital Haveli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age between 18 and 60 years.
2. Resident of District Haveli, Azad Kashmir for more than last 1 year.
3. Consent to participate in the study.
4. Exposure to war-related stressors (self-reported).

Exclusion Criteria:

1. Age below 18 or above 60 years
2. Ingestion of vit D 200,000 IU in last 3 months.
3. Known diagnosis of primary hyperparathyroidism or sarcoidosis (i.e. conditions pre-disposing to vitamin D hypersensitivity)
4. Residents outside of District Haveli.
5. Baseline corrected serum calcium concentration >2.65 mmol/L
6. Unwillingness to provide informed consent.
7. Medical conditions or medication use affecting vitamin D metabolism.
8. Pregnant or lactating mothers
9. On anti-tuberculosis medicines
10. HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental arm in which we will give the active Vitamin D to participants; the intervention will be the Vitamin D in its active form 200,00 IU 25(OH)D3.route of administration is oral.	Dietary supplement: 25 hydroxy cholecalciferol (Vitamin D) /25(OH)D3.; 5 mg (200,000 IU) vitamin D3 in 1 ml ethyl oleate Pharmaceutical form: Solution of vitamin D3 in ethyl oleate, 0.75% w/v. three doses will be given orally every a month apart.
Placebo Comparator: placebo arm in which we will give the placebo; olive oil will be the placebo medicine. the placebo medicine have similar taste and quantity. the route of administration is oral.	Dietary supplement: Placebo; Olive oil in 1 ml ethyl oleate with no vitamin D3 content

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Allostatic load is a measure of physiological dysregulation caused by the accumulated impact of chronic stress on the body. Systolic pressure ≥ 150 mmHg, and 120 to 149 mmHg < 120 mmHg Diastolic blood pressure ≥ 90 mmHg, 80 to 89 mmHg < 80 mmHg	4 months
lipid profile	Total cholesterol ≥ 240 mg/dL, 200 to 239 mg/dL < 200 mg/dL HDL < 40 mg/dL 40 to 59 mg/dL, > 60 mg/dL Total /HDL cholesterol ≥ 6 5 to < 6 < 5	4 months
body mass index BMI	Body mass index (BMI) ≥ 30 kg/m2, and 2 25 to < 30 kg/m2 18 to < 25 kg/m	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of vitamin D for the assessment and effect on the allostatic load and chronic stress among the residents of line of control.	Vitamin D level will give us the clue for the supplementation effect and effect on the allostatic load and chronic stress. vitamin D normal range 30 ng/dl and above vitamin D insufficiency 20-29 ng/dl vitamin D deficiency less than 20 ng/dl	4 months
Hip waist ratio (HRR) cm2	Waist hip ratio (women) ≥ 0.85cm2 > 0.80 to < 0.85cm2 ≤ 0.80cm2 Waist hip ratio (men) ≥ 1.0cm2 > 0.95 to < 1.0cm2 ≤ 0.95cm2	4 months

Collaborators and Investigators

• Sponsor: University of the Punjab
• Investigators: Principal Investigator: jawwad AF kayani, PhD, University of the Punjab

Publications and helpful links

General Publications

• Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Kostenberger M, Tmava Berisha A, Martucci G, Pilz S, Malle O. Vitamin D deficiency 2.0: an update on the current status worldwide. Eur J Clin Nutr. 2020 Nov;74(11):1498-1513. doi: 10.1038/s41430-020-0558-y. Epub 2020 Jan 20.
• Bunting BA, Smith BH, Sutherland SE. The Asheville Project: clinical and economic outcomes of a community-based long-term medication therapy management program for hypertension and dyslipidemia. J Am Pharm Assoc (2003). 2008 Jan-Feb;48(1):23-31. doi: 10.1331/JAPhA.2008.07140.
• Casseb GAS, Kaster MP, Rodrigues ALS. Potential Role of Vitamin D for the Management of Depression and Anxiety. CNS Drugs. 2019 Jul;33(7):619-637. doi: 10.1007/s40263-019-00640-4.

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2023
• Primary Completion (Estimated): August 25, 2024
• Study Completion (Estimated): September 15, 2024

Study Registration Dates

• First Submitted: October 12, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcifediol; Alfacalcidol; Hydroxycholecalciferols
• Other Study ID Numbers: D/142/FIMS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No