To assess the efficacy of two weeks eucaloric ketogenic diet on GH and IGF-I levels in acromegaly patients.
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of two weeks eucaloric ketogenic diet on GH and IGF-I
levels in acromegaly patients. The primary endpoints are the difference in GH
and IGF-I levels before and after 2 weeks of ketogenic diet.
Secondary outcome
The secondary objective of the study is to evaluate whether ketogenic diet,
might have a:
* blood glucose lowering effect;
* positive effect on the insulin secretion;
* induces weight loss;
* positive effect on the lipid profile, especially on triglycerides and free
fatty
acids
* broad safety range
This secondary objectives are measured by the following efficacy and safety
parameters:
Blood biochemistry: (t0 =baseline, t1= week 1 and t2= week 2)
* IGF-1 levels
* GH levels
* IGF-BP1 levels
* Fasting plasma glucose, insulin, HbA1c levels, HOMA-IR
* Total cholesterol, HDL-cholesterol and LDL-cholesterol levels
* Triglycerides, free fatty acids
* AST, ALT, alkaline phosphatase, gamma-glutamyltransferase, lactate
dehydrogenase (LDH)
Note: all the following laboratory evaluations will be performed at the study
site.
Urine: (t1= week 1 and t2= week 2)
One voided sample of urine will be collected at the study site. One dipstick
strip is used to measure ketones.
Vital signs: (t0 =baseline, t1= week 1 and t2= week 2)
Pulse rate and blood pressure were measured after 5 minutes of rest in the
seated position at the outpatient clinic.
Anthropometric measurements: (t0 =baseline, t1= week 1 and t2= week 2)
Height and body weight were obtained at the outpatient clinic; patients will be
weighted clothed without shoes. Body composition will be assessed at the
outpatient clinic by Body Impedance Assessment. Waist-to-hip ratio were
measured as follows. The waist was defined as the minimal abdominal
circumference located midway between the lower rib margin and the iliac crest.
The hip was defined as the wides circumference over the great trochanters.
Circumferences were measured with the subjects in the standing position using
flexible tape measure and maintaining close contact with the skin without
compression of underlying tissues.
One questionnaire: (t1= week 1 and t2= week 2) will be filled out at the
outpatient clinic(*Vragenlijst gebruik en effecten dieetproduct*. In this
questionnaire we assess the ease of use, safety and compliance.
One food diary (t0 =baseline, t1= week 1 and t2= week 2) will be filled out
at the outpatient clinic. In this questionnaire we assess therapy compliance.
Background summary
In patients without biochemical control with LA-SSA monotherapy on maximum
doses for at least 6 months, there are currently three therapy options: add or
switch to Pegvisomant therapy, transsphenoidal surgery or radiotherapy.
However, several studies shown in healthy subjects that when restricted
carbohydrates are ingested, the decrease in portal vein insulin concentration
can also lead to a reduction in IGF-I synthesis by the liver. The contribution
of a eucaloric ketogenic diet, could provide the same decrease in IGF-I and GH
levels in acromegaly patients. When ketogenic diet in acromegaly patients could
provide normalisation of IGF-I levels and/or GH levels, it can be considered as
fourth therapy option in patients without biochemical control with LA-SSA
monotherapy. However, the effect of eucaloric ketogenic diet on IGF-I and GH
secretion in acromegaly patients has not been studied yet.
Study objective
To assess the efficacy of two weeks eucaloric ketogenic diet on GH and IGF-I
levels in acromegaly patients.
Study design
This will be a single-centre, prospective, proof-of-concept intervention study.
Intervention
All ten subjects received eucaloric ketogenic diet for two weeks (see figure 1
protocol). During this ad libitum ketogenic diet, emphasis is placed on
polyunsaturated and monounsaturated fats (diet margarines, oils, fish, nuts).
Moreover, we also supplement the diet with polyunsaturated and monounsaturated
fats and therefore this diet is eucaloric (contains about the same number of
calories subjects use each day).
Study burden and risks
Study participants will have 3 visits to the outpatient clinic over a period of
2 weeks. This comes down to 180 minutes in total. During this visits physical
exam will be performed, 2 blood tubes of 2,5 cc and one voided sample of urine
will be collected and two questionnaires will be filled out of 60 minutes in
total. The usual burden for a single patient is 2-outpatient visits over a
period of 1 year, which takes about 60 minutes in total and with the same
volume of blood per visit.
Administering a eucaloric ketogenic diet did not produce any significant side
effects for a longer period of time[1, 2]. Therefore, we expect it is safe to
use a ketogenic diet for two weeks in our subjects. When ketogenic diet in
acromegaly patients could provide normalisation of IGF-I levels and/or GH
levels, it can be considered as fourth therapy option in patients without
biochemical control with LA-SSA monotherapy on maximum doses for at least 6
months. Eucaloric ketogenic diet combined with LA-SSA and/or Pegvisomant
therapy has potentially also the advantage that a lower LA-SSA or Pegvisomant
dose is required to normalize IGF-I and/or GH levels .
's Gravendijkwal 230
Rotterdam 3015 CE
NL
's Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
-Written informed consent male or female aged * 18.
-Documentation supporting the diagnosis of acromegaly based on elevated GH and/or IGF-I levels due to a pituitary tumor
-The patient is treated with lanreotide Autogel or octreotide long-acting release (LAR) on maximum doses for at least 6 months and has a serum IGF-I level above 120% of the age- and sex adjusted normal limits.
-Subjects must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period and willing to return to the clinic for the follow-up evaluation as specified in the protocol.
Exclusion criteria
- Has undergone pituitary surgery or radiotherapy within 6 months prior to study entry.
- It is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
- Has a history of epilepsy
- Has been treated with any unlicensed drug within the last 30 days before study entry.
- Has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
- Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subjects safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
- Diabetes type 1 or diabetes type 2 and using insulin
- Use of systemic corticosteroids within 60 days prior to screening
- Females of childbearing potential must be using contraception (we do not perform a pregnancy test), otherwise excluded from the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL64773.078.18 |
| OMON | NL-OMON27621 |