Estimation of a Maintaining Daily Jarlsberg Cheese-dose
Condition: Maintenance Dose; Osteocalcin; Vitamin K Deficiency
MeSH terms: Vitamin K Deficiency
Study type: Interventional

Summary: 
      The study objective is to estimate a maintaining daily dose of Jarlsberg cheese in healthy
      pre-menopausal women obtaining an increase in the osteocalcin level of at least 10% after 6
      weeks on maximum efficacy dose (MED) of Jarlsberg cheese.

      1.4: Population and sampling The study population consists of Healthy Voluntary (HV) women
      between 20 years and pre-menopausal age.

      The study will be performed as a one-dimensional, within-patient, 3-level Response Surface
      Pathway (RSP) designed trial with individually adjustment of the dose. Each design period
      will be 3 weeks. Only HVs obtaining an increase in the osteocalcin level ≥ 10% from baseline
      after 6 weeks on the MED of 57g Jarlsberg cheese daily will be offered to participate in this
      de-escalation study.
    

Detailed description: 
      The recruited HV women fulfilled the inclusion without the exclusion criteria for the study
      will undergo a screening clinical investigation. The participants will be asked to avoid use
      of other cheese than the one allocated to in the study, but eat as usual. One week later, the
      first clinical investigation in the study will take place including blood sampling and
      measurement of visual signs. The HV women verified to fulfil the criteria for participation
      and signed the informed consent form will be included in the study. During this first
      clinical investigation in the study denoted as Day 0, the participants receive a study
      identification number. The daily intake of cheese will be 57g/day . The trial cheese can be
      consumed with other food at breakfast, lunch or other meals during the day.

      The participants meet for new clinical investigations every third week with measurement of
      visual signs and blood sampling. The first 12 HVs finalized 6 weeks with daily intake of 57 g
      Jarlsberg cheese obtaining an increase in the osteocalcin level from baseline ≥10% will be
      offered participation in this de-escalation study. The results of the osteocalcin analysis
      after 6 weeks will be ready within one week and the HVs continue on unchanged cheese dose.
      The HVs participating in this de-escalation study will be included in this part after 7
      weeks. The remaining HVs will continue the Jarlsberg cheese intake as prescribed in protocol
      HV-Jarlsberg/III.

      The de-escalation study consists of three design level each of three weeks duration. The
      analysis of the osteocalcin level taken after three weeks will be ready within one week
      later. This measurement will be the background for change in the dose for the next design
      level. During this first week after the three-week period, the HVs will continue on the same
      cheese dose until the results from the osteocalcin analysis is available.

      The HVs included in this de-escalation study will receive a reduced daily dose of Jarlsberg
      cheese for three weeks in the first design level. The reduction in the daily Jarlsberg cheese
      dose will be individually calculated. Assume a given HV obtained X % increase in the
      osteocalcin level during the previous six weeks with a daily dose of 57g. The reduction in
      the daily Jarlsberg cheese dose for the first design level will be x% [(57*X)/100]. If the
      osteocalcin level reduces > 10% from the 6-weeks level after 3 weeks on the reduced dose, the
      dose will be increased for this HV on the second design level. In case the obtained change in
      the osteocalcin level is ± 10%, the dose will be unchanged. If the osteocalcin level
      increases > 10 % from the 6-week level, the cheese dose will be reduced for this HV in the
      second design level. The size of the dose increase or decrease from the first to the second
      design level depending on the change in the osteocalcin level from the 6-week level and
      calculated in accordance with the RSP procedure. The change in the osteocalcin level during
      the second design level will be the basis for calculation of the dose to be used in the third
      design level. The same procedure as described for the dose-change from the first to the
      second design level will be used. Clinical investigation and blood sampling will be performed
      every third week. Osteocalcin and vitamin K will be analysed every third week whereas the
      haematological and biochemical analysis will be performed at baseline and after 6 and 18
      weeks of cheese intake.

      The main variable in this study will be osteocalcin measured in serum blood and percent
      increase in osteocalcin from baseline. Additionally, carboxylated and under carboxylated
      Osteocalcin and the ratio OR = [Carboxylated / Under Carboxylated] osteocalcin in serum will
      be central together with the K2 variants MK-7, 8, 9, 9(4H) and vitamin K1. Triglyceride, LDL-
      and HDL cholesterol, vitamin D and vital signs will be secondary variables. As safety
      variables, haematological- and biochemical variables and adverse events (AE) will be recorded
      at each visit.

      In accordance with the development of the RSP-procedure, 12 HVs will be included in the study
      and participate in all the three design levels.
    

Intervention name(s): Jarlsberg Cheese
Intervention type(s): Dietary Supplement
Intervention description(s): Oral daily intake of Jarlsberg cheese
Intervention model: Single Group Assignment
Intervention model description: Within-patient Response Surface Pathway
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: Jarlsberg cheese