Profylactic Treatment for Patients in Risk Osteoporosis

Study Overview
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Brief Summary
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The aim is to compare the daily intake of Calsium (Ca) + vitamin D with and without daily optimal efficacy dose (OED) of Jarlsberg on Bone Mineral Density (BMD) and bone markers (BM) to Osteopeni patients (OP). The study population consists of OP-patients of post-menopausal women and men above 55 years of age. OP patients are defined as patients with a T-score below 0.0, but larger than -2.5. The study will be performed as a randomized, single-blinded Norwegian multicentre trial with stratified semi-cross-over design with gender and site as stratification factors. The OP-patients included in the study will be allocated to one of the two treatment groups by block randomization with random block size between 2 and 6. Women in post-menopausal age have a daily OED Jarlsberg of 45 gram and men in the same age interval have a daily OED of 55 gram. The main response variable will be the change in Bone Mineral Density (BMD),total Osteocalcin (tOC) and different bone markers (BM). Participants, who fulfil the inclusion criteria, do not meet any of the exclusion criteria and willing to give informed consent to participate will be included and receiving 40µg vitamin D and 500 mg Ca tablets per day, but asked not to eat Jarlsberg cheese the following week. During this week demographic data, bloodsampling for measurement of Osteocalcin and BM and diet registration will be performed.In the clinical study, all the included patients will continue with Ca+ vitamin D, but half of the patient will additionally receive daily OED of Jarlsberg cheese. After 16 weeks, all the patients will receive both Ca+vitamin D and OED of Jarlsberg for addionally 16 weeks. The total duration of the study will be 32 weeks for the patients initially allocated to Jarlsberg and 48 weeks for those allocated only to Ca+vitamin D. The patients will be investigated initially and every 16 weeks. A total of 30 patients will be included in each of the two groups.

Detailed Description
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Aim To estimate the effect of daily optimal efficacy dose (OED) of Jarlsberg cheese on BMD and bone markers to patients with Osteopeni (OP). To compare daily intake of Calsium (Ca) and vitamin D with and without OED of Jarlsberg on BMD and bone markers to OP patients. To compare daily intake of Ca and vitamin D with and without OED of Jarlsberg on Time-to-Osteoporotic (TTO) treatment is recommended. Study population consists of OP-patients of post-menopausal women and men above 55 years of age. OP patients are defined as patients with a T-score below 0.0, but larger than -2.5. Women in post-menopausal age have a daily OED Jarlsberg of 45 gram and men in the same age interval have a daily OED of 55 gram. The cheese will be delivered in package of 250 gram with slices of 15.625gram. 45 gram represents 3 slices; 55 gram 4 slices. All the included patients will receive 20µg vitamin D and 1000 mg Ca. Half of the patients will receive vitamin D and Ca-tablets plus Jarlsberg cheese (Treatment group I) and other half only vitamin D and Ca-tablets (Treatment group II). Design: The study will be performed as a randomized, single-blinded Norwegian multicentre trial with stratified semi-cross-over design with gender and site as stratification factors. Patients included in the study will be allocated to one of the two treatment groups by block randomization with random block size between 2 and 6. Main variables: The main response variable will be the change in Bone Mineral Density (BMD).The secondary variables will be total Osteocalcin (tOC), carboxylated osteocalcin (cOC), the osteocalcin ratio and different bone markers (BM). Additionally, the K2 vitamers MK-7, MK-8, MK-9, and MK-9(4H) will be used as explanatory variable together with the Interleukins IL-1β, IL6, IL8, IL10 and the Cytokines TNF-α, NF-ƙβ (RANK-L), OPG and TGF-β . Diet registration as controlling variables and HbA1C, Lipids, biochemical variables will be used as supporting variables. The Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) will be used for registration of Adverse Events (AE) and toxicity score at every investigation visit. Study procedure: Participants, who fulfil the inclusion criteria, do not meet any of the exclusion criteria and willing to give informed consent to participate will be included in a screening period of one week. During this screening week, all the possible participants will receive 40µg vitamin D and 500 mg Ca tablets per day, but asked not to eat Jarlsberg cheese. BMD measurements will be taken at the start of the screening week. Patients with a negative BMD T-score >-2.5 will be included in the study. All demographic data, social factors, history of disease and vital signs will be recorded at baseline. The participating patients will be given a Diet-App on the web or mobile phone for registration of the daily food intake during four first consecutively days after baseline. Blood samples for measurements of Osteocalcin, BM and vitamin K will be taken fastening in the morning. Additionally, blood samples for measuring biochemical variables, HbA1C, Lipids, Interleukins and Cytokines, will be recorded. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 used for measuring and classifying the tolerability and toxicity will be recorded as well. The patients will be given a compliance & activity form and asked to write down the daily intake of treatment medicine, Jarlsberg cheese and hours of physical activities. Clinical part: The patients will be allocated (1:1) to vitamin D + Ca-tablets ± OED of Jarlsberg cheese. All the participants will get new delivery of vitamin D and Ca-tablets every four weeks. The patients allocated to Jarlsberg will additionally receive Jarlsberg cheese. The patients will receive a compliance & activity form and asked to fill in every day. All the patients meet for new visits at week4, week 16, and week 32. Patients allocated to only vitamin D + Ca tablets at baseline well additionally meet for visits at week 20 and week 48. At all these visits blood samples for measurement of Osteocalcin, BM and PTH will be drawn fasting in the morning, and concomitant medication and treatment compliance recorded. The main visit will be performed every 16 weeks. New DXA screening will be performed. Patients obtaining a BMD T-score ≤ -2.5 will discontinue the study and switched to antiresorptive treatment plus daily OED of Jarlsberg cheese. The daily food intake during four consecutively days will be recorded on the Diet-App. Blood samples for measurements of Osteocalcin, CTX-1, PINP, BALB and PTH will be drawn fastening in the morning at every visits. Furthermore, blood samples for measuring and biochemical variables, HbA1C and Lipids, will be recorded. The CTCAE will be recorded as well.After the first 16 weeks, the patients allocated to only Ca + vitamin D will additionally receive OED of Jarlsberg cheese out the study. The visit at Week 32 and Week 48 will be the last observation for the patients initially allocated to Jarlsberg and controls, respectively. In addition to the mentioned variables, blood samples for measurement of Interleukins and Cytokines will be performed. All the patients completed the study will be offered to continue the daily intake of OED Jarlsberg cheese. These patients will be followed up one year after the last visit with a new DXA and a blood sampling for measurements of Osteocalcin level and BM. Sample size: With a significance level of 5%, a power of 90% and a Clinically Relevant Difference (CRD) of one time the Standard Deviation in change of BMD, at least 24 patients in each group must finalize the study. With an expected drop-out rate of 25%, 30 patients in each group must be included.

Official Title
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The Effect on Bone Marker and Body Mineral Density (BMD) of Daily Jarlsberg Cheese Intake in Risk Patient for Osteoporosis

Conditions
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Osteopenia or Osteoporosis

Intervention / Treatment
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* Dietary Supplement: Calsium, Vitamin D, Jarlsberg cheese


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteopeni patients (OP) of both genders above 55 years of age. OPs are defined as patients with T-score below 0.0 but larger than -2.5. Exclusion Criteria: • Eating disorder Known gastrointestinal disorder. Abnormal liver or kidney function. Diabetes mellitus type I. Diabetes type II without sufficient control. Suffering from verified cancer. Under systemic treatment with corticosteroids or other immunosuppressive drugs the last 3 weeks before start of the trial treatment. Under active antiresorptive treatment or anabolic treatment. Participating in another clinical trial with pharmaceuticals the last six weeks before start of this trial treatment. Known milk product allergy. Not able to understand information. Do not want or not able to give written consent to participate in the study.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients are randomised (1:1) into to parallel groups and followed up in 16 weeks. All the patients are switched to the same treatment for the following 16 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment 1<br>1000 mg Calcium tablets + 20µg vitamin D and optimal efficacy dose of Jarlsberg cheese | Dietary Supplement: Calsium, Vitamin D, Jarlsberg cheese<br>* Oral<br>|
| Active Comparator: Treatment 2<br>1000 mg Calcium tablets + 20µg vitamin D | Dietary Supplement: Calsium, Vitamin D, Jarlsberg cheese<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density | g/cm2 | Week 0 | 
| Bone Mineral Density | g/cm2 | Week 16 | 
| Bone Mineral Density | g/cm2 | Week 32 | 
| Bone Mineral Density | g/cm2 | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Osteocalcin | ng/ml | week 0 | 
| Osteocalcin | ng/ml | week 4 | 
| Osteocalcin | ng/ml | week 16 | 
| Osteocalcin | ng/ml | week 20 | 
| Osteocalcin | ng/ml | week 32 | 
| Osteocalcin | ng/ml | week 48 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 0 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 4 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 16 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 20 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 32 | 
| Procollagen type 1 N-terminal propeptide (PINP) | ng/ml | Week 48 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 0 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 4 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 16 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 20 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 32 | 
| Cross-linked C-telopeptide type I collagen (CTX) | ng/ml | week 48 | 
| Bone specific ALP (BALB) | ng/ml | Week 0 | 
| Bone specific ALP (BALB) | ng/ml | Week 4 | 
| Bone specific ALP (BALB) | ng/ml | Week 16 | 
| Bone specific ALP (BALB) | ng/ml | Week 20 | 
| Bone specific ALP (BALB) | ng/ml | Week 32 | 
| Bone specific ALP (BALB) | ng/ml | Week 48 |