NCT01877512

Brief Summary

Rationale: Abnormally low and high levels of insulin-like growth factor-I (IGF-I) are both associated with increased metabolic risk. Since (U-shaped) associations of IGF-I, within the normal range, have also been found with cardiovascular risk factors and disease in the general population, it would be interesting to investigate if this association can also be found in growth hormone deficient (GHD) adults treated with Growth Hormone (GH). This could be of interest for endocrinologists prescribing GH in clinical practice because strict dosing may become even more important. Next to that, scientific evidence for clinical practice is wanted. Objective: Next to cardiovascular risk factors (main objectives: body composition and lipid profile; secondary objectives: remainder) we investigate the effect on glucose metabolism, physical performance, and neuropsychological functioning of different levels of IGF-I in GH treated GHD men and women. Study design: Open-label randomized trial. Study population: At least 32 subjects, both childhood as adult onset GHD men and women, receiving GH treatment for at least one year, with an age between 20 and 65 years. Intervention: At entry subjects are already receiving GH treatment according to general clinical practice, and are expected to demonstrate an IGF-I concentration of 0 - 1 SD score (SDS) (normal dose). The group of men and group of women will be randomized to receive either a decrease of their regular dose of GH treatment (IGF-I target level of -2 - -1 SDS) (low dose), or an increase of their regular dose, (IGF-I target level of 1 - 2 SDS) (high dose) for at least 24 weeks.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started May 2013

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2013

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 11, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 13, 2013

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
Last Updated

May 7, 2014

Status Verified

May 1, 2014

Enrollment Period

11 months

First QC Date

June 11, 2013

Last Update Submit

May 6, 2014

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change in cardiovascular risk (body composition and lipid profile)

    24 weeks

Secondary Outcomes (4)

  • Change in cardiovascular risk (inflammatory markers, vascular stiffness, endothelial function, presence of the metabolic syndrome)

    24 weeks

  • Change in physical performance (muscle strength, physical activity)

    24 weeks

  • Change in glucose metabolism (fasting and 2hr postprandial glucose, insulin resistance)

    24 weeks

  • Change in neuropsychological functioning (QoL, cognition, mood)

    24 weeks

Study Arms (2)

Low dose Growth Hormone

ACTIVE COMPARATOR

Halve of the group of men and group of women will receive a decrease of their regular dose of Growth Hormone treatment, with the IGF-I target level of -2 - -1 SD score (low dose=LD).

Drug: Change in daily dosage of Growth Hormone

High dose Growth Hormone

ACTIVE COMPARATOR

Halve of the group of men and group of women will receive an increase of their regular dose of Growth Hormone treatment, with the IGF-I target level of 1 - 2 SD score (high dose=HD).

Drug: Change in daily dosage of Growth Hormone

Interventions

Also known as: Change in daily dosage of Somatropin
High dose Growth HormoneLow dose Growth Hormone

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Ongoing surveillance at our centre (VUmc)
  • Stable substitution therapy for other pituitary hormone deficiencies

You may not qualify if:

  • Subjects with a craniopharyngioma as cause of their GHD or pituitary deficiencies
  • Contraindications for the use of GH treatment
  • (Receiving treatment for) malignant disease (in the past)
  • Participation in other studies
  • Subjects, who in the opinion of the investigator, are unsuitable in any other way to participate in this study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU University Medical Center

Amsterdam, PO Box 7057, 1007 MB, Netherlands

Location

Related Publications (2)

  • van Bunderen CC, Meijer RI, Lips P, Kramer MH, Serne EH, Drent ML. Titrating Growth Hormone Dose to High-Normal IGF-1 Levels Has Beneficial Effects on Body Fat Distribution and Microcirculatory Function Despite Causing Insulin Resistance. Front Endocrinol (Lausanne). 2021 Feb 9;11:619173. doi: 10.3389/fendo.2020.619173. eCollection 2020.

  • van Bunderen CC, Deijen JB, Drent ML. Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency. Health Qual Life Outcomes. 2018 Jul 6;16(1):135. doi: 10.1186/s12955-018-0963-2.

MeSH Terms

Conditions

Dwarfism, PituitaryCardiovascular DiseasesMetabolic SyndromeMotor Activity

Condition Hierarchy (Ancestors)

DwarfismBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesBone Diseases, EndocrineHypopituitarismPituitary DiseasesHypothalamic DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesEndocrine System DiseasesInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesBehavior

Study Officials

  • Madeleine L. Drent, MD PhD

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

June 11, 2013

First Posted

June 13, 2013

Study Start

May 1, 2013

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

May 7, 2014

Record last verified: 2014-05

Locations