Hypovitaminosis DPhase 3GEHF-VitDNCT01315366
Hypovitaminosis D : A Link Between Bone/Mineral and Fat/Fuel Metabolism
A Phase 3 study testing Euro D and Ci-CalD and Euro D, Ci-CalD in people with Hypovitaminosis D and Insulin Resistance, run by American University of Beirut Medical Center at 1 site in Lebanon.
Trial summary
The optimal dose of vitamin D needed to optimize beneficial effects on musculoskeletal outcomes remains to be defined. Equally unclear is the impact of vitamin D on fuel metabolism and insulin sensitivity in human subjects. Read more about this study
- Who is it for?
- Ages 65 to 95 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypovitaminosis D, Insulin Resistance, Obesity
- What is being tested?
- Euro D and Ci-CalD and Euro D, Ci-CalD
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 257 participants
- Where
- 1 siteLebanon
- Study dates
- Jan 2011to Jul 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 95 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Elderly subjects (> or equal to 65 years old)without any disease mentioned in the exclusion criteria.
- BMI ≥ 25Kg/meters squared
Who cannot join
- Exclusion criteria include: diabetes, subjects with impaired glucose tolerance on medication, presence of a chronic disease or major organ failure such as severe heart failure, kidney or liver failure, conditions or intake of medications known to affect bone metabolism, rickets or osteomalacia, history of kidney stones, a baseline vitamin D level of less than 10 ng/ml and history of fragility fractures or an overall fracture risk based on FRAX of >10% .
- Subjects with impaired glucose tolerance on no medications will not be excluded.
- The classification of individuals as diabetics or having impaired glucose tolerance will be based on the American Diabetes Association criteria for diagnosis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase III Study on the Effect of Vitamin D Supplementation on Indices of Mineral and Musculoskeletal Metabolism and on Parameters of Glucose and Fuel Metabolism in Elderly Subjects
The optimal dose of vitamin D needed to optimize beneficial effects on musculoskeletal outcomes remains to be defined. Equally unclear is the impact of vitamin D on fuel metabolism and insulin sensitivity in human subjects. Thus, the overall objective of this proposal is to test the hypothesis that in ambulatory overweight elderly individuals, vitamin D administration at doses higher than currently recommended will:
- Have a salutary effect on parameters of glucose and fuel metabolism. It will thus decrease indices of insulin resistance, improve lipid profile, and decrease markers of cardiovascular disease including adipokines, inflammatory cytokines, and markers of cell adhesion.
- Have a superior effect on indices of mineral and musculoskeletal metabolism, including bone remodeling markers, lean mass, and bone mineral density.
We will investigate whether this effect is modulated by entry status of vitaminD and PTH as detailed below
Read the detailed description
It has become increasingly recognized that low vitamin D levels are prevalent worldwide and to a more severe degree in the Middle East. Low vitamin D levels are associated with an increased risk of osteoporotic fractures, and of chronic conditions such as autoimmune disorders, diabetes, cancer, and the metabolic syndrome. Obese individuals are more likely to have low vitamin D levels, and in some studies obesity was a risk factor for fractures in both the young and elderly. Our group has investigated the impact of vitamin D therapy in the young, and preliminary data suggest that doses exceeding the currently updated recommended estimated average requirement (EAR) of 400IU for that age group may be more beneficial for bone health. The updated EAR recommendations by the IOM for any age group, although believed to cover the needs of all individuals in each age group, are limited by the lack of good evidence supporting such recommendations. Therefore, to-date, the optimal dose of vitamin D for both the young and elderly is unknown.
Two hundred and fifty elderly (age≥65 years), overweight (BMI ≥25kg/m2) non-diabetic individuals, will be recruited through outpatient clinics that investigators may have access to at American University of Beirut-Medical Center (AUB-MC), Hotel Dieu de France (HDF) and Rafic Hariri University Hospital (RHUH), and will be randomized after a pre-screen, in a double-blinded fashion, to receive 500 IU or the equivalent of 3357 IU of vitamin D3 daily for one year. Clinical information, exercise questionnaires will be obtained at 0 and 12 months.In addition, subjects partaking in the original study will be offered the option to participate in the validity and reliability study of a food frequency questionnaire to assess dietary intakes of Ca, vitamins D and K, and to participate in the vascular study evaluating the relation of the above nutrients with vascular parameters. Information on educational level, insurance status, dietary, sunscreen use, sun exposure and skin pigmentation will be obtained at baseline. Information on falls, trauma, history of fractures and medications will be obtained at each visit (0, 3, 6 and 12 months). The measurement of height, weight, BMI, waist, hip, waist/hip ratio, mid arm circumference, mid-calf circumference and muscle strength of the subject, enrolled in the study, will be triplicated on each visit at 0,3,6 and 12 months. Blood pressure and heart rate will be measured at screening, baseline, 3 months, 6 months and 12 months. Blood will be drawn at baseline, 3, 6 and 12 months for measurement of serum creatinine, calcium, phosphorous, alkaline phosphatase, 25-OHD, 1,25(OH)2D, PTH, indices of bone remodeling (osteocalcin and crosslaps), and a second morning void urine specimen will be collected for Ca/Cr. Insulin resistance will be measured using the McAuley as well as HOMA and QUCKI indices. We will also measure serum levels of adipokines (adiponectin, leptin), DLK1-Pref1, inflammatory markers (CRP, IL-6) and adhesion molecules (sICAM, sVCAM). We will characterize polymorphisms of genes affecting mineral metabolism such as VDR, CaSR,ER and CYP2R1, and will measure adiponectin R expression from subcutaneous fat and muscle biopsies that will be obtained at 0 and 12 months.Bone density scans of Lumbar Spine, Femoral Neck, Total Hip, Total Body, Sub Total Body, body composition and hip structural analyses parameters as well as TBS variables for the spine will be obtained at the baseline and at 12 months of the study. A visit at 9 months will be scheduled to supply subjects with Ci-cal D and Euro D, and to ensure compliance. IRB approval and consent forms will be obtained. An independent Data and Safety Monitoring Board will be asked to review serious adverse events and if needed may be asked to review unblinded data at recruitment of 30%, 60% and 100% of study subjects and of serious adverse events forms throughout the study duration.Repeated measures analyses will be used to evaluate differences in outcomes of interest between the two treatment groups and time effect within each treatment arm.
- Conditions
- Hypovitaminosis D, Insulin Resistance, Obesity, Osteoporosis
- Being tested
- Euro D and Ci-CalD, Euro D, Ci-CalD
- Keywords
- Vitamin D, Elderly, Cardiovascular profile, Insulin resistance, Gene polymorphisms
- Medical subject headings
- Vitamin D Deficiency, Insulin Resistance, Obesity, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Euro D and Ci-CalDDietary supplement
Also called Europharm
Ci-Cal D (1000mg/day) and vitamin D (500IU/day) daily, plus a supplement of vitamin D3 (20,000 IU/wk) for one year.
Euro D, Ci-CalDDietary supplement
Also called EuroPharm
Ci-Cal D(1000mg/day) and vitamin D (500IU/day) Ci-CalD daily, plus a weekly placebo Euro D supplement for one year.
| Study group | Role | What they receive |
|---|---|---|
| High dose vitamin D | Active comparator | Ci-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a supplement of vitamin D3 EuroD (20,000 IU/wk) for one year. Receives: Dietary Supplement: Euro D and Ci-CalD |
| Low dose Vitamin D | Placebo comparator | Ci-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a weekly placebo (EURO D Placebo) supplement for one year. Receives: Dietary Supplement: Euro D, Ci-CalD |
What is being measured
The primary outcome is the main question the study is designed to answer.
The HOMA index of insulin resistance
A full assessment of insulin resistance will be performed,using the HOMA, McAuley and QUICKI indices.
The impact of vitamin D on all outcomes of interest will be assessed by treatment arms and then in sub-group analyses:
- by baseline levels of vit D-PTH at study entry: Vitamin D< 20 ng/ml-PTH>76pg/ml; vitamin D<20ng/ml and PTH<76 pg/ml, vitamin D>20ng
- by gender
Measured: 1 year
Bone mineral density (BMD) at the spine,hip and total body measured by DXA and bone turnover markers (Osteocalcin and cross laps).
We will measure the bone mineral density at the spine, hip and total body. We will also test the bone turnover markers as osteocalcin and cross laps.
Measured: 1 year
Secondary outcomes (11)
Insulin, C- peptide, Fasting glucose, Chemistries, Vitamin D metabolites, Vitamin D binding protein, Urinary Ca/Cr ratio ,serum lipids,inflammatory markers(IL-6, CRP),adhesion molecules (sVCAM), GLA-OC and GLU-OC.
Gamma-Carboxyglutamatic Osteocalcin (GLA-OC) and Undercarboxylated Osteocalcin (GLU-OC).
Measured: 1 year
Body fat mass and body lean mass measured by DXA
Measured: 1 year
Serum DLk1 levels
Serum DLK1 levels Preadipocyte factor 1 (Pref-1), also known as delta like protein (Dlk1), is a molecule that belongs to the Notch Delta family of signaling molecules, epidermal growth factor (EGF)-like super family, and possesses several isoforms, some circulating, also termed Fetal antigen 1 (FA1).
Measured: 1 year
Adiponectin Receptor expression and Leptin from subcutaneous fat and muscle biopsies at baseline and follow-up.
Measured: 1 year
Morphologic bone assessment gathered defined by techniques incorporated into BMD acquisition scan image: Hip structural analyses parameters (Cortical thickness, Cross-sectional moment of inertia, section modulus) and trabecular bone structure (TBS)
Measured: 1 year
Mc Auley Index of insulin resistance by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Measured: 1 year
BMD at the hip and body composition by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Measured: 1 year
Bone turnover markers by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Measured: 1 year
Bone mineral density (BMD) at the spine measured by DXA
Measured: 1 year
Adiponectin Receptor expression from subcutaneous fat and muscle biopsies
Measured: 1 year
Morphologic bone assessment gathered defined by techniques incorporated into BMD acquisition image:Hip structural analyses parameters and trabecular bone structure by subgroups of subjects divided by polymorphisms of genes affecting mineral metabolism
Genes affecting mineral metabolism are VDR, ER, CaSR, and CYP2R1 gene polymorphisms
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2011 (estimated)
- Study startJan 2011
- Primary completionAug 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Hypovitaminosis DStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 257 participants (actual)
Sponsor and investigators
- Lead sponsor
- American University of Beirut Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Hotel Dieu de France Hospital, Rafic Hariri University Hospital
- Responsible party
- Principal investigator, Dr. Ghada El-Hajj Fuleihan, American University of Beirut Medical Center
- Investigators
- Ghada El Hajj Fuleihan, MD, MPH, Principal investigator, American University of Beirut Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01315366
- Sponsor's protocol ID
- AUBMC-GE-HF-1
- Other IDs
- AUBMC-IM-GE-HF-20
- Acronym
- GEHF-VitD
- Status last verified
- Mar 2015
- First submitted
- 2 Feb 2011
- Last updated
- 20 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fuleihan GE, Deeb M. Hypovitaminosis D in a sunny country. N Engl J Med. 1999 Jun 10;340(23):1840-1. doi: 10.1056/NEJM199906103402316. No abstract available.
PubMed 10366324El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006 Feb;91(2):405-12. doi: 10.1210/jc.2005-1436. Epub 2005 Nov 8.
PubMed 16278262Arabi A, Zahed L, Mahfoud Z, El-Onsi L, Nabulsi M, Maalouf J, Fuleihan Gel-H. Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls. Bone. 2009 Dec;45(6):1091-7. doi: 10.1016/j.bone.2009.07.074. Epub 2009 Jul 30.
PubMed 19647104Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006 Sep;260(3):245-54. doi: 10.1111/j.1365-2796.2006.01685.x.
PubMed 16918822Arabi A, Baddoura R, Awada H, Salamoun M, Ayoub G, El-Hajj Fuleihan G. Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect? Bone. 2006 Aug;39(2):268-75. doi: 10.1016/j.bone.2006.01.140. Epub 2006 Feb 21.
PubMed 16495164Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008 Jun 23;168(12):1340-9. doi: 10.1001/archinte.168.12.1340.
PubMed 18574092Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, Yanovski JA. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab. 2004 Mar;89(3):1196-9. doi: 10.1210/jc.2003-031398.
PubMed 15001609Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007 Jun;92(6):2017-29. doi: 10.1210/jc.2007-0298. Epub 2007 Mar 27.
PubMed 17389701Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005 May;28(5):1228-30. doi: 10.2337/diacare.28.5.1228. No abstract available.
PubMed 15855599Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med. 2009 Jan;26(1):19-27. doi: 10.1111/j.1464-5491.2008.02636.x.
PubMed 19125756Fliser D, Stefanski A, Franek E, Fode P, Gudarzi A, Ritz E. No effect of calcitriol on insulin-mediated glucose uptake in healthy subjects. Eur J Clin Invest. 1997 Jul;27(7):629-33. doi: 10.1046/j.1365-2362.1997.1520699.x.
PubMed 9263752Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care. 2007 Apr;30(4):980-6. doi: 10.2337/dc06-1994. Epub 2007 Feb 2.
PubMed 17277040Gannage-Yared MH, Azoury M, Mansour I, Baddoura R, Halaby G, Naaman R. Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women. J Endocrinol Invest. 2003 Aug;26(8):748-53. doi: 10.1007/BF03347358.
PubMed 14669830Fay TN, Jacobs I, Teisner B, Poulsen O, Chapman MG, Stabile I, Bohn H, Westergaard JG, Grudzinskas JG. Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid; preliminary observations in fetal and maternal tissues. Eur J Obstet Gynecol Reprod Biol. 1988 Sep;29(1):73-85. doi: 10.1016/0028-2243(88)90167-0.
PubMed 3224746Abdallah BM, Jensen CH, Gutierrez G, Leslie RG, Jensen TG, Kassem M. Regulation of human skeletal stem cells differentiation by Dlk1/Pref-1. J Bone Miner Res. 2004 May;19(5):841-52. doi: 10.1359/JBMR.040118. Epub 2004 Jan 19.
PubMed 15068508
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study on the Effect of Vitamin D Supplementation on Indices of Mineral and Musculoskeletal Metabolism and on Parameters of Glucose and Fuel Metabolism in Elderly Subjects
- ClinicalTrials.gov ID
- NCT01315366
- Acronym / sponsor ID
- GEHF-VitD / AUBMC-GE-HF-1
- Conditions
- Hypovitaminosis D, Insulin Resistance, Obesity, Osteoporosis
- Keywords
- Vitamin D, Elderly, Cardiovascular profile, Insulin resistance, Gene polymorphisms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 257 participants (actual)
- Lead sponsor
- American University of Beirut Medical CenterUniversity, hospital or other
- Collaborators
- Hotel Dieu de France Hospital, Rafic Hariri University Hospital
- Study start
- Jan 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 15 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The optimal dose of vitamin D needed to optimize beneficial effects on musculoskeletal outcomes remains to be defined. Equally unclear is the impact of vitamin D on fuel metabolism and insulin sensitivity in human subjects. Thus, the overall objective of this proposal is to test the hypothesis that in ambulatory overweight elderly individuals, vitamin D administration at doses higher than currently recommended will:
- Have a salutary effect on parameters of glucose and fuel metabolism. It will thus decrease indices of insulin resistance, improve lipid profile, and decrease markers of cardiovascular disease including adipokines, inflammatory cytokines, and markers of cell adhesion.
- Have a superior effect on indices of mineral and musculoskeletal metabolism, including bone remodeling markers, lean mass, and bone mineral density.
We will investigate whether this effect is modulated by entry status of vitaminD and PTH as detailed below
Detailed description
It has become increasingly recognized that low vitamin D levels are prevalent worldwide and to a more severe degree in the Middle East. Low vitamin D levels are associated with an increased risk of osteoporotic fractures, and of chronic conditions such as autoimmune disorders, diabetes, cancer, and the metabolic syndrome. Obese individuals are more likely to have low vitamin D levels, and in some studies obesity was a risk factor for fractures in both the young and elderly. Our group has investigated the impact of vitamin D therapy in the young, and preliminary data suggest that doses exceeding the currently updated recommended estimated average requirement (EAR) of 400IU for that age group may be more beneficial for bone health. The updated EAR recommendations by the IOM for any age group, although believed to cover the needs of all individuals in each age group, are limited by the lack of good evidence supporting such recommendations. Therefore, to-date, the optimal dose of vitamin D for both the young and elderly is unknown.
Two hundred and fifty elderly (age≥65 years), overweight (BMI ≥25kg/m2) non-diabetic individuals, will be recruited through outpatient clinics that investigators may have access to at American University of Beirut-Medical Center (AUB-MC), Hotel Dieu de France (HDF) and Rafic Hariri University Hospital (RHUH), and will be randomized after a pre-screen, in a double-blinded fashion, to receive 500 IU or the equivalent of 3357 IU of vitamin D3 daily for one year. Clinical information, exercise questionnaires will be obtained at 0 and 12 months.In addition, subjects partaking in the original study will be offered the option to participate in the validity and reliability study of a food frequency questionnaire to assess dietary intakes of Ca, vitamins D and K, and to participate in the vascular study evaluating the relation of the above nutrients with vascular parameters. Information on educational level, insurance status, dietary, sunscreen use, sun exposure and skin pigmentation will be obtained at baseline. Information on falls, trauma, history of fractures and medications will be obtained at each visit (0, 3, 6 and 12 months). The measurement of height, weight, BMI, waist, hip, waist/hip ratio, mid arm circumference, mid-calf circumference and muscle strength of the subject, enrolled in the study, will be triplicated on each visit at 0,3,6 and 12 months. Blood pressure and heart rate will be measured at screening, baseline, 3 months, 6 months and 12 months. Blood will be drawn at baseline, 3, 6 and 12 months for measurement of serum creatinine, calcium, phosphorous, alkaline phosphatase, 25-OHD, 1,25(OH)2D, PTH, indices of bone remodeling (osteocalcin and crosslaps), and a second morning void urine specimen will be collected for Ca/Cr. Insulin resistance will be measured using the McAuley as well as HOMA and QUCKI indices. We will also measure serum levels of adipokines (adiponectin, leptin), DLK1-Pref1, inflammatory markers (CRP, IL-6) and adhesion molecules (sICAM, sVCAM). We will characterize polymorphisms of genes affecting mineral metabolism such as VDR, CaSR,ER and CYP2R1, and will measure adiponectin R expression from subcutaneous fat and muscle biopsies that will be obtained at 0 and 12 months.Bone density scans of Lumbar Spine, Femoral Neck, Total Hip, Total Body, Sub Total Body, body composition and hip structural analyses parameters as well as TBS variables for the spine will be obtained at the baseline and at 12 months of the study. A visit at 9 months will be scheduled to supply subjects with Ci-cal D and Euro D, and to ensure compliance. IRB approval and consent forms will be obtained. An independent Data and Safety Monitoring Board will be asked to review serious adverse events and if needed may be asked to review unblinded data at recruitment of 30%, 60% and 100% of study subjects and of serious adverse events forms throughout the study duration.Repeated measures analyses will be used to evaluate differences in outcomes of interest between the two treatment groups and time effect within each treatment arm.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High dose vitamin D | Active comparator | Dietary Supplement: Euro D and Ci-CalDCi-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a supplement of vitamin D3 EuroD (20,000 IU/wk) for one year. |
| Low dose Vitamin D | Placebo comparator | Dietary Supplement: Euro D, Ci-CalDCi-Cal D (1000mg/day) and vitamin D (500IU/day) Ci-Cal D daily, plus a weekly placebo (EURO D Placebo) supplement for one year. |
Who may qualify
- Ages
- 65 to 95 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Elderly subjects (> or equal to 65 years old)without any disease mentioned in the exclusion criteria.
- BMI ≥ 25Kg/meters squared
Key exclusion criteria (3 listed)
- Exclusion criteria include: diabetes, subjects with impaired glucose tolerance on medication, presence of a chronic disease or major organ failure such as severe heart failure, kidney or liver failure, conditions or intake of medications known to affect bone metabolism, rickets or osteomalacia, history of kidney stones, a baseline vitamin D level of less than 10 ng/ml and history of fragility fractures or an overall fracture risk based on FRAX of >10% .
- Subjects with impaired glucose tolerance on no medications will not be excluded.
- The classification of individuals as diabetics or having impaired glucose tolerance will be based on the American Diabetes Association criteria for diagnosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Euro D and Ci-CalDAlso: EuropharmCi-Cal D (1000mg/day) and vitamin D (500IU/day) daily, plus a supplement of vitamin D3 (20,000 IU/wk) for one year. | Dietary supplement | High dose vitamin D |
| Euro D, Ci-CalDAlso: EuroPharmCi-Cal D(1000mg/day) and vitamin D (500IU/day) Ci-CalD daily, plus a weekly placebo Euro D supplement for one year. | Dietary supplement | Low dose Vitamin D |
Primary outcome
The HOMA index of insulin resistance
Time frame: 1 year
A full assessment of insulin resistance will be performed,using the HOMA, McAuley and QUICKI indices. The impact of vitamin D on all outcomes of interest will be assessed by treatment arms and then in sub-group analyses: * by baseline levels of vit D-PTH at study entry: Vitamin D< 20 ng/ml-PTH>76pg/ml; vitamin D<20ng/ml and PTH<76 pg/ml, vitamin D>20ng * by gender
Bone mineral density (BMD) at the spine,hip and total body measured by DXA and bone turnover markers (Osteocalcin and cross laps).
Time frame: 1 year
We will measure the bone mineral density at the spine, hip and total body. We will also test the bone turnover markers as osteocalcin and cross laps.
11 secondary outcomes
Insulin, C- peptide, Fasting glucose, Chemistries, Vitamin D metabolites, Vitamin D binding protein, Urinary Ca/Cr ratio ,serum lipids,inflammatory markers(IL-6, CRP),adhesion molecules (sVCAM), GLA-OC and GLU-OC.
Time frame: 1 year
Body fat mass and body lean mass measured by DXA
Time frame: 1 year
Serum DLk1 levels
Time frame: 1 year
Adiponectin Receptor expression and Leptin from subcutaneous fat and muscle biopsies at baseline and follow-up.
Time frame: 1 year
Morphologic bone assessment gathered defined by techniques incorporated into BMD acquisition scan image: Hip structural analyses parameters (Cortical thickness, Cross-sectional moment of inertia, section modulus) and trabecular bone structure (TBS)
Time frame: 1 year
Mc Auley Index of insulin resistance by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Time frame: 1 year
BMD at the hip and body composition by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Time frame: 1 year
Bone turnover markers by subgroups of patients divided by polymorphisms of genes affecting mineral metabolism (VDR, ER, CaSR, and CYP2R1 gene polymorphisms).
Time frame: 1 year
Bone mineral density (BMD) at the spine measured by DXA
Time frame: 1 year
Adiponectin Receptor expression from subcutaneous fat and muscle biopsies
Time frame: 1 year
Morphologic bone assessment gathered defined by techniques incorporated into BMD acquisition image:Hip structural analyses parameters and trabecular bone structure by subgroups of subjects divided by polymorphisms of genes affecting mineral metabolism
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
- Background: PubMed 10366324Fuleihan GE, Deeb M. Hypovitaminosis D in a sunny country. N Engl J Med. 1999 Jun 10;340(23):1840-1. doi: 10.1056/NEJM199906103402316. No abstract available.
- Background: PubMed 16278262El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006 Feb;91(2):405-12. doi: 10.1210/jc.2005-1436. Epub 2005 Nov 8.
- Background: PubMed 19647104Arabi A, Zahed L, Mahfoud Z, El-Onsi L, Nabulsi M, Maalouf J, Fuleihan Gel-H. Vitamin D receptor gene polymorphisms modulate the skeletal response to vitamin D supplementation in healthy girls. Bone. 2009 Dec;45(6):1091-7. doi: 10.1016/j.bone.2009.07.074. Epub 2009 Jul 30.
- Background: PubMed 16918822Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006 Sep;260(3):245-54. doi: 10.1111/j.1365-2796.2006.01685.x.
- Background: PubMed 16495164Arabi A, Baddoura R, Awada H, Salamoun M, Ayoub G, El-Hajj Fuleihan G. Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect? Bone. 2006 Aug;39(2):268-75. doi: 10.1016/j.bone.2006.01.140. Epub 2006 Feb 21.
- Background: PubMed 18574092Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, Kinkeldei J, Boehm BO, Weihrauch G, Maerz W. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008 Jun 23;168(12):1340-9. doi: 10.1001/archinte.168.12.1340.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ghada El Hajj Fuleihan, MD, MPH principal investigator
American University of Beirut Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Euro D and Ci-CalD and Euro D, Ci-CalD in people with Hypovitaminosis D and Insulin Resistance, run by American University of Beirut Medical Center at 1 site in Lebanon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Lebanon. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The HOMA index of insulin resistance (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01315366, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.