Estimation of Minimum Efficacy Daily Dose (MTDD) of Jarlsberg Cheese in Healthy Women in Order to Obtain Needed Level of Osteocalcin: A Phase I Dose-finding Study
Estimation of Minimum Efficacy Daily Dose (MTDD) of Jarlsberg Cheese in Healthy Women in Order to Obtain Needed Level of Osteocalcin: A Phase I Dose-finding Study
Aim: To estimate an oral administered recommended minimum efficacy daily dose (MED) of Jarlsberg cheese in order to obtain the needed increased level of Osteocalcin defined as the ratio [Carboxylated / Under Carboxylated] Osteocalcin.
Study population: Healthy Voluntary (HV) women between 20 years and pre-menopausal age.
Design: Open and randomised two-dimensional single-centre trial with 3-level between-patient Response Surface Pathway (RSP) design in the first dimension and 3-level within-patient RSP design in the secondary dimension.
The recruited HV women fulfil the inclusion without the exclusion criteria for the study will undergo a clinical investigation and blood sampling. The participants will be asked to avoid use of other cheese, but eat as usually. One week later, the first clinical investigation will take place including blood sampling. The HV women verified to fulfil the criteria for participation and signed the informed consent form will be included in the study. The trial treatment consisting of a given gr/day Jarlsberg cheese will start the day after this investigation, denoted as Day 0, and the participants receiving a study identification numbers. They will be instructed not to change eating habit except replace use of other chees with Jarlsberg.
The cheese can be consumed with other food at breakfast and/or lunch. The dose of Jarlsberg cheese per day is fixed per participant and varies from 20 gram per day to 180 gram per day with a mid-dose of 100gr/day. The three patients included at the first design level will all receive this mid-dose of 100gr/day. Clinical investigation and blood sampling after start of the treatment, will be performed after 3, 4, and 5 weeks and the ratio [Carboxylated / Under Carboxylated] Osteocalcin will be calculated. This increased Osteocalcin Ratio (OR) based on the results obtained by the blood sampling at week 3 will be classified in five groups and used for determination of the Jarlsberg cheese dose for the five HV women at design level 2. The classifications of increased OR used are: increased OR < 0.5 classifies as Low; 0.5 ≤ increased OR ≤ 0.9 classifies as Moderate Low; 0.9 < increased OR < 1.1 classifies as Suitable; 1.1≤increased OR≤1.5 classifies as Moderate High; increased OR > 1.5 classifies as High. In case the increased OR is found Low or Moderate Low, the daily dose of Jarlsberg cheese will be reduced for the participants at the second design level. If increased OR classifies as Suitable the same dose as at design level 1 will be recommended applied at the second level and if increased OR classifies as moderate High or High, the Jarlsberg cheese-dose will be increased.
The same procedure based on the results obtained from the five participants at the second design level will be used to determine the daily Jarlsberg-dose for the seven HV women at design level 3. With randomization of the recommended cheese-doses at one design level to be used in the next, the between-patient Response-Surface-Pathway (RSP) design-arm is applied.
The within-patient RSP design-arm is applied and related to the duration of the cheese intake. All the participants will consume Jarlsberg cheese during minimum three weeks. Participants obtaining an increased OR ≥ 1 can stop the study. If not, they have to continue until this limit is reached or until maximum five weeks.
Inclusion Criteria:
Exclusion Criteria: