Obesity, Osteoarthritis, Type 2 Diabetes
Conditions
Keywords
Randomized Controlled Trial, Acetyl L-Carnitine, Postmenopausal Women, Oxidative Stress
Brief summary
OA is a degenerative bone disease more common in postmenopausal women. Diabetes and obesity are common risk factors for the development of OA. The common symptoms include pain and disability of the affected joint, leading to mobility issues. Acetyl L-carnitine due to its known anti-inflammatory, chondroprotective, and improved insulin-sensitizing effects may help in alleviating the symptoms and progression of OA in obese diabetic postmenopausal women.
Detailed description
Osteoarthritis (OA) is a chronic degenerative joint disease that commonly affects older adults and is associated with pain, stiffness, reduced mobility, and disability. The coexistence of obesity and type 2 diabetes mellitus may aggravate the progression and severity of OA through metabolic dysfunction, chronic low-grade inflammation, oxidative stress, and altered adipokine profiles. Postmenopausal women are particularly vulnerable because hormonal changes contribute to increased inflammation, obesity, insulin resistance, and joint degeneration. Acetyl L-Carnitine is a naturally occurring compound involved in mitochondrial energy metabolism. Previous studies have demonstrated anti-inflammatory, antioxidant, and metabolic benefits of Acetyl L-Carnitine, including improvements in insulin resistance, lipid metabolism, oxidative stress, and inflammatory cytokine production. Experimental studies have also suggested chondroprotective effects through enhancement of cartilage matrix synthesis and mitochondrial function. This double-blind, placebo-controlled randomized clinical trial will enroll 100 obese, diabetic, postmenopausal women with radiologically confirmed osteoarthritis. Participants will be randomly assigned to receive either Acetyl L-Carnitine (1.5 g twice daily) or placebo for 12 weeks in addition to conventional osteoarthritis treatment. Clinical outcomes will include assessment of osteoarthritis symptoms using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), radiological severity using the Kellgren-Lawrence grading system, perceived stress, and depression, anxiety and stress scores. Laboratory outcomes will include glycemic profile, lipid profile, insulin resistance markers, inflammatory biomarkers (CRP and IL-6), oxidative stress markers, adipokines, stress hormones, and complete blood count parameters. The study seeks to determine whether Acetyl L-Carnitine supplementation can improve clinical, metabolic, inflammatory, and radiological outcomes in obese, diabetic, postmenopausal women with osteoarthritis.
Interventions
Acetyl L-Carnitine capsules, 1.5 g administered orally twice daily (total daily dose 3 g) after meals for 12 weeks in addition to conventional osteoarthritis treatment.
DRUGPlacebo
Matching placebo capsules administered orally twice daily for 12 weeks in addition to conventional osteoarthritis treatment.
Sponsors
Khyber Medical University Peshawar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Masking description
This is a double-blind placebo-controlled trial. Participants will receive either Acetyl L-Carnitine or placebo. Investigators, healthcare providers, participants, and outcome assessors will remain unaware of treatment allocation throughout the study.
Intervention model description
Participants will be randomly assigned to one of two parallel groups: conventional treatment plus placebo or conventional treatment plus Acetyl L-Carnitine (1.5 g twice daily) for 12 weeks. Outcomes will be assessed at baseline and after intervention.
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 55-65 years 2. Duration of menopause 2-15 years. 3. Duration of diabetes 5-15 years 4. BMI Obese ≥30 kg/m2 5. Grade≥2 K\&L on radiologic examination
Exclusion criteria
* Female patients with osteoarthritis meeting the following criteria will be excluded from the study; 1. Age˂55 ˃65yrs 2. Post-menopausal duration of ˂2yrs 3. Duration of diabetes ˂ 5years 4. Patients with alcohol abuse, asthma, cardiac disease, chronic gastric problems (malabsorption, crohn's disease chronic diarrhea), non-diabetes related renal disease,ovariectomy, rheumatoid arthritis or other rheumatic inflammatory diseases, smoking 5. Patients taking steroids (oral/ injections) 6. Patients with a history of parathyroid and thyroid surgery/dysfunction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum C-Reactive Protein Concentration | Baseline and Week 12 | Change in Serum C-Reactive Protein (CRP) Concentration (mg/L) from baseline following 12 weeks of Acetyl L-Carnitine supplementation. |
| Fasting Blood Glucose Concentration | Baseline and Week 12 | Change in fasting blood glucose levels (mg/dL) from baseline following 12 weeks of intervention. |
| Glycated Hemoglobin (HbA1c) Percentage | Baseline and Week 12 | Change in HbA1c levels (%) from baseline following 12 weeks of intervention. |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Baseline and Week 12 | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score from baseline following 12 weeks of intervention. |
| Fasting Serum Insulin Concentration | Baseline and Week 12 | Change in fasting serum insulin concentration (µIU/mL) from baseline following 12 weeks of intervention. |
| Serum Leptin Concentration | Baseline and Week 12 | Change in serum leptin concentration (ng/mL) from baseline following 12 weeks of intervention. |
| Serum Adiponectin Concentration | Baseline and Week 12 | Change in serum adiponectin concentration (µg/mL) from baseline following 12 weeks of intervention. |
| Serum Adrenocorticotropic Hormone (ACTH) Concentration | Baseline and Week 12 | Change in serum ACTH concentration from baseline following 12 weeks of intervention |
| Serum Malondialdehyde (MDA) Concentration | Baseline and Week 12 | Change in serum malondialdehyde levels as a marker of oxidative stress from baseline following 12 weeks of intervention. |
| Serum Advanced Glycation End Products (AGEs) Concentration | Baseline and Week 12 | Change in serum AGEs levels from baseline following 12 weeks of intervention. |
| WOMAC Osteoarthritis Index total Score | Baseline and Week 12 | Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline following 12 weeks of intervention. |
| Kellgren-Lawrence Radiographic Grade | Baseline and Week 12 | Change in osteoarthritis radiographic severity assessed by the Kellgren-Lawrence grading system from baseline following 12 weeks of intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interleukin-6 (IL-6) | Baseline and Week 12 | Change in serum IL-6 concentration from baseline following 12 weeks of Acetyl L-Carnitine supplementation. |
Countries
Pakistan
Contacts
PRINCIPAL_INVESTIGATORDr Safia Bibi, PhD*
Khyber Medical University Peshawar, Pakistan
PRINCIPAL_INVESTIGATORDr Mohsin Shah, PhD
Khyber Medical University Peshawar, Pakistan
PRINCIPAL_INVESTIGATORDr Zia Ullah, PhD
Khalifa Gul Nawaz Teaching Hospital
Outcome results
None listed