Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05434806 |
| Other study ID # |
HV-Jarlsberg/ID |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 19, 2023 |
| Est. completion date |
June 15, 2023 |
Study information
| Verified date |
May 2024 |
| Source |
Meddoc |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Aim: To estimate OED of Jarlsberg cheese and the stabilized level of serum Osteocalcin in
healthy elderly men and women.
Study population consists of healthy men at least 65 years old and healthy post-menopausal
women.
Trial treatment: Daily intake of Jarlsberg cheese within a window of [20 - 100] gram/day and
a starting dose of 40 gram/day Design: The study will be performed as an open, two-armed
between-patient randomized Response Surface Pathway (RSP) study with three design level and
skewed starting dose.
Study procedure: HVs who fulfils the inclusion criteria, do not meet any of the exclusion
criteria and willing to give informed consent to participate will receive an appointment for
starting the study one week later. All demographic data, social factors and history of
disease will be recorded. The design consists of three design levels and measurement taken at
screening, after four weeks daily intake of the decided dose of Jarlsberg cheese. At
screening, after four weeks of daily intake of Jarlsberg cheese, a physical examination
,CTCAE and concomitant medication will be performed. Additionally, blood sampling will be
taken at screening and after four weeks for measurements of Osteocalcin, PINP, CTX, BALP,
vitamin K and common laboratory variables.
Sample size: Fifteen female and 15 male HVs divided on 3 design levels.
Description:
Aim: To estimate OED of Jarlsberg cheese and the stabilized level of serum Osteocalcin in
healthy elderly men and women.
Study population consists of healthy men at least 65 years old and healthy post-menopausal
women.
Trial treatment: Daily intake of Jarlsberg cheese within a window of [20 - 100] gram/day and
a starting dose of 40 gram/day
Design: The study will be performed as an open, two-armed between-patient randomized Response
Surface Pathway (RSP) study with three design level and skewed starting dose. One arm
consists of healthy post-menopausal women and the other of healthy men at least the age of
65years. The two arms will be performed separately in parallel with identical RSP-design.
The aim is to estimate OED based on percent change in the Osteocalcin level from baseline to
4 weeks of daily intake of Jarlsberg cheese. The main outcome variable will be categorized in
the following four categories:
1. Low increase in the Osteocalcin level: < 10% the last 4 weeks
2. Moderate Low increase in the Osteocalcin level: [10 - 30% > the last 4 weeks
3. Moderate High increase in the Osteocalcin level: [30 - 50% > the last 4 weeks
4. High increase in the Osteocalcin level: ≥ 50% the last 4 weeks
The design consists of three dose levels. Three HVs in each gender arm will be included in
the first design level and all receiving the starting dose of Jarlsberg cheese every day in
four weeks. The increase in osteocalcin from baseline to four weeks will be used to calculate
the doses for the five HVs of both gender in the second design level. Five patients will be
included in the second design level and given the daily doses of Jarlsberg cheese recommended
from the results obtained in the first design level. Seven patients will be included on the
third design level and given the daily doses of Jarlsberg cheese recommended from the results
obtained in the second design level.
The OMT for healthy women in pre-menopausal age was previously estimated at 57-gram Jarlsberg
cheese per day. It is unknown if this OED will be larger for men and increase / decrease with
age. The initial dose window in this study was set to [20 - 100] gram based on the previous
dose-response study in healthy pre-menopausal women.
Based on our prior knowledge, the Osteocalcin follows a quadratic function in Jarlsberg
cheese dose. The Osteocalcin seem to increase with increasing dose until a maximum (OED) and
reduces for higher intake of the cheese. OED might be below the midpoint of the initial dose
window of 60gr/day. To optimize the estimation procedure, the skewed starting dose of 40g/day
or 2,5 slices of Jarlsberg cheese will be chosen. This gives an adjusted starting dose window
of [20 - 60] gr/day. In case the results from all the three HVs of a given gender in the
first design level reports an increase < 10% in the Osteocalcin level, the RSP-procedure
recommend a maximum escalation in the daily intake of Jarlsberg cheese for the five new HVs
of the given gender in the second design level. The new starting dose-window will then be
change with the previously used starting dose as lower boundary. In the present study the
adjusted dose-window for the second design level will then be [40 - 70] g/day with the new
starting dose of 55g/day. In case the result from the three HVs in the first design level
obtained an increase in the osteocalcin level between 10% and 30%, the dose to be used in the
second design level will be 45g/day with a dose-window of [40 - 50] g/day. Based on the
results obtained at the second design level, the similar procedure will be used to calculate
the dose used at the third design level. In case the results obtained at on the design level
recommend different doses to be used for the next level, the common RSP procedure will be
follows.
Randomization: The three HVs allocated to first design level in each of the two parallel
gender arms will all receive 40 g/day in four weeks with osteocalcin measurements after every
three weeks. A response-dependant block randomisation procedure will be used based on the
results obtained after three weeks. This will be performed for the second design level based
on the results obtained in the first design level and at the third design level based on the
obtained results in the second.
Main variables: The main response variable will be the change in the total Osteocalcin level
after four weeks from baseline. The ratio R0= [Carboxylated / Under carboxylated]
Osteocalcin, the bone markers Collagen (CTX-1), Procollagen (PINP) and bone specific ALP
(BALB) will be used as secondary variables. Vitamin K1 and K2 including the different
fractions MK-7, 8, 9 and 9/4H 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.
Study procedure: HVs who fulfils the inclusion criteria, do not meet any of the exclusion
criteria and willing to give informed consent to participate will receive an appointment for
starting the study one week later. All demographic data, social factors and history of
disease will be recorded at screening. The design consists of three design levels and
measurement taken at screening, after four weeks daily intake of the decided dose of
Jarlsberg cheese. All the participants will be asked not to change anything in their common
intake of food during the study except for replacing other cheese with the received daily
dose of Jarlsberg. At screening, after four weeks of daily intake of Jarlsberg cheese, a
physical examination including registration of vital signs, CTCAE and concomitant medication
will be performed. Additionally, blood sampling will be taken at screening and after four
weeks for measurements of Osteocalcin, PINP, CTX, BALP, vitamin K and common laboratory
variables.
Sample size: Fifteen female and 15 male HVs divided on 3 design levels [3 + 5 + 7] =15 must
be included, perform, and complete the study. In case of a fourth design level, the sample
size increases to [3 + 5 + 7 +9] =24. This is the minimum number of patients recommended used
in a RSP model.
