Condition category
Neonatal Diseases
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 2

Trial website

Contact information



Primary contact

Dr Bart Koot


Contact details

Department of Pediatrics
Suite H7-250
Meibergdreef 9
1105 AZ

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Cholic acid treatment in Peroxisomal Biogenesis Disorders (Zellweger spectrum): biochemical and clinical effects


Study hypothesis

Cholic acid supplementation in mild Zellweger spectrum patients improves intestinal fat absorption and growth by increasing the amount of intraluminal bile acids, thus promoting micellar solubilization. In addition, we hypothesize that cholic acid supplementation improves liver function and alleviates neurological symptoms by suppressing the endogenous bile acid synthesis and stimulating bile flow, thus decreasing the production of potentially toxic and cholestatic bile acid intermediates.

Neurological milestones will be performed by a trained observer not blinded for the patients’ treatment phase. Measurements of weight and height, fibroscan liver elasticity measurements and laboratory tests will be performed by operators blinded for the patients’ treatment phase.

Ethics approval

1. Medical Ethical Committee AMC, March 2011 ref: MEC 10/276
2. Centrale Commissie Mensgebonden Onderzoek (CCMO), December 2010, ref: NL33339.018.10

Study design

Single-centre open label pilot study

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Zellweger spectrum disorder


Investigational product:
Cholic acid is the predominant human bile acid. In this study, cholic acid will be supplemented for 9 months in a regular dose. No placebo will be used.

Use of co-intervention:
Changes in diet during the study period will be recorded. Use of possible hepatotoxic medication should be avoided if an equally effective alternative drug is available. All changes in co-medication will be recorded.

Dosages, dosage modifications and method of administration:
Cholic acid will be administered in doses of 15 mg/kg/day in 2 or 3-divided doses daily orally during meals. In case of incomplete suppression of bile acid intermediates in week 36 the dosage will be increased to 20 mg/kg/day in 2 or 3 divided doses daily. Frequency of administration depends on the number of capsules needed daily, objective is to administer an equal dose over the day.

Cholic acid can de administered as capsules or liquid depending on the participant’s preference. Capsules of 250 and 50 mg will allow accurate dosing at 15 mg/kg/day in patients with body weight above 6 kilogram. In case the dosage is increased to 20 mg/kg/day or patients weighting less than 6 kg are included capsules will be prepared adapted to the patients’ weight by the AMC pharmacy. For this cutom-made preparation the same drug substance and addatives as described in the CMC will be used to prepare the drug product. As this is not a standardized preparation procedure, the storage life will be limited to 6 months after custom made preparation.

The medication will be provided by Asklepion Pharmaceuticals and it will be shipped to the pharmacy of the AMC pharmacy who will be responsible for capsule preparation and distribution of the product. At the end of the (premature) end of the studies the remaining medicinal product will be taken in by the treating physician and returned to the AMC pharmacy.

Intervention type



Not Specified

Drug names

Primary outcome measures

1. Degree of suppression of endogenous bile acid synthesis [Decrease in urine 3 alpha,7 alpha -dihydroxycholestanoic acid (DHCA) and 3 alpha,7alpha,12 alpha - trihydroxycholestanoic acid (THCA) bile acid intermediates and increase in FGF-19]
2. Increase in normal primary bile acids [increase in urine cholic acid (CA)]
3. Change in fat soluble vitamins levels (T= 24 weeks versus T= 42 weeks)
4. Change in weight gain (weight-for-height percentile) (T= 36 weeks versus T=72 weeks)
5. Change total body length growth rate (cm/year; only in those with remaining growth potential)
6. Feasiibility and side effects of cholic acid supplementation; diarrhea, vomiting, liver dysfunction and others
Measured at 0, 24, 36, 48, 72 weeks

Secondary outcome measures

1. Change in seizure frequency
2. Change in the obtained developmental mile stones
3. Change serum transminases and γ-glutamyltrans- peptidase levels
4. Change in fibroscan liver elasticity measurements
5. Change in liver protein synthesis
6. Change in markers of peroxisomal / mitochondrial functioning
Measured at 0, 24, 36, 48, 72 weeks

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Zellweger spectrum disorder
2. At least one of the following hallmarks:
2.1. Steatorrhea
2.2. Elevated transaminases
2.3. Growth retardation
2.4. Neurological symptoms

Participant type


Age group




Target number of participants


Participant exclusion criteria

Short life expectancy (severe multiple organ dysfunction at the time of diagnosis)

Recruitment start date


Recruitment end date



Countries of recruitment

Netherlands, United States of America

Trial participating centre

Department of Pediatrics
1105 AZ

Sponsor information


Emma Paeditric Hosptial (Netherlands)

Sponsor details

Meibergdreef 9 (TKs0-253)
1105 AZ

Sponsor type

Hospital/treatment centre



Funder type

Hospital/treatment centre

Funder name

Emma Paediatric Hospital (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes