Growth Hormone + Liraglutide for Metabolic Health Improvement

Overseen By Pamela U. Freda, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Columbia University

Must not be taking: Glucocorticoids, Hormonal supplements

Disqualifiers: Diabetes, Malignancy, Pancreatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 3 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a randomized, placebo-controlled, cross-over study with 4 arms. Healthy and GH deficient adults ages 18-45 years will be studied. Arms will consist of 21-day treatment periods and be separated by 8-week washout periods. Subjects will receive, in random order: i) GH alone, ii) GH with liraglutide, iii) liraglutide alone and iv) placebo. Each phase of the study will consist of a 7-day baseline period including 2 days of testing and 21 days on therapy with visits on days 2, 7, 14 and 21. Testing before, during and at the completion of each arm will include blood sampling and assessments of insulin resistance, energy expenditure and body composition.

Will I have to stop taking my current medications?

Yes, participants must not be on any prescription medications or drugs that could affect growth hormone or IGF-1 levels, or for weight loss, within 6 months of enrollment.

Is the combination of Growth Hormone and Liraglutide generally safe for humans?

Growth hormone (GH) has been used safely for over 40 years, with a wide safety margin, though it requires monitoring for side effects like swelling, increased blood sugar, and other rare conditions. No data suggests GH increases cancer risk, and studies show no significant adverse effects in children treated with GH. ^{1 2 3 4 5}

What makes the Growth Hormone + Liraglutide drug unique for metabolic health improvement?

This treatment combines growth hormone (which helps with growth and metabolism) and liraglutide (a medication that can help with weight loss and blood sugar control), offering a novel approach by targeting both growth and metabolic pathways simultaneously, which is different from using either component alone. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Growth Hormone + Liraglutide for improving metabolic health?

Research shows that growth hormone treatment can reduce body fat, increase lean body mass, and improve metabolic health in adults with growth hormone deficiency. Additionally, growth hormone has been effective in reducing visceral fat in patients with certain conditions, suggesting potential benefits for metabolic health. ^{8 9 10 11 12}

Are You a Good Fit for This Trial?

Adults aged 18-45, both healthy and those with growth hormone deficiency, can join this trial. Healthy participants should be either overweight or lean without serious medical conditions. GH deficient subjects must not have had prior GH therapy for a year and need normal thyroid and adrenal function.

Inclusion Criteria

Current non-smoker

I am overweight with a BMI between 25-34.9 and have a waist size of at least 102 cm if male, or 88 cm if female.

I am overweight/obese with no other medical conditions.

Exclusion Criteria

I do not have other pituitary, liver, or kidney diseases.

I have a history of cancer, diabetes, thyroid issues, or pancreatitis.

Recent dieting, weight change >5%, pregnancy or lactation or heavy exercise

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

7-day baseline period including 2 days of testing

1 week

2 visits (in-person)

Treatment

Participants receive nightly subcutaneous injections of study medications or placebo for 21 days

3 weeks

4 visits (in-person) on days 2, 7, 14, and 21

Washout

8-week washout period between treatment arms

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Growth Hormone
• Growth Hormone and Liraglutide
• Liraglutide
• Placebo

Trial Overview The study tests the effects of growth hormone (GH) alone, liraglutide alone, both combined, and placebo on metabolism in adults. It's a randomized study where each participant tries all treatments in different periods with breaks in between.

How Is the Trial Designed?

Group I: Growth hormone and liraglutide Active Control 1 Intervention

GH will be administered as one nightly subcutaneous self-injection at 11pm at a dose of 0.03 mg/kg/day in healthy and 0.5 mg in male and 0.6 mg in female GHD subjects. Liraglutide will be administered by subcutaneous injection taken by subjects beginning at a dose at 0.6 mg nightly from 9-11 pm and escalated in 0.6 mg increments weekly as tolerated to a final dose of 1.8 mg nightly. Injections will be performed from the night of day 0 to the night of day 20.

Group II: Growth hormone Active Control 1 Intervention

GH will be administered as one nightly subcutaneous self-injection at 11pm at a dose of 0.03 mg/kg/day in healthy and 0.5 mg in male and 0.6 mg in female GHD subjects. Injections will be performed from the night of day 0 to the night of day 20.

Group III: Liraglutide Active Control 1 Intervention

Liraglutide will be administered by subcutaneous injection taken by subjects beginning at a dose at 0.6 mg nightly from 9-11 pm and escalated in 0.6 mg increments weekly as tolerated to a final dose of 1.8 mg nightly. Injections will be performed from the night of day 0 to the night of day 20.

Group IV: Placebo Placebo Group 1 Intervention

Placebo will be administered as one nightly subcutaneous self-injection at 9-11pm from the night of day 0 to the night of day 20.

Growth Hormone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Somatropin for:

• Growth hormone deficiency
• Turner syndrome
• Prader-Willi syndrome
• Chronic kidney disease
• Short stature due to Noonan syndrome
• Short stature due to Turner syndrome
• HIV-associated wasting

Approved in European Union as Somatropin for:

• Growth hormone deficiency
• Turner syndrome
• Prader-Willi syndrome
• Chronic kidney disease
• Short stature due to Noonan syndrome
• Short stature due to Turner syndrome

Approved in Canada as Somatropin for:

• Growth hormone deficiency
• Turner syndrome
• Prader-Willi syndrome
• Chronic kidney disease
• Short stature due to Noonan syndrome
• Short stature due to Turner syndrome

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

A study involving 135 adults with adult growth hormone deficiency (AGHD) found that both depot growth hormone (GH) given every 14 days and daily GH injections significantly reduced trunk and visceral fat, with the depot form showing a 3.2% decrease in trunk fat compared to no treatment.

Both treatment methods increased lean body mass and had similar side effect profiles, indicating that the depot GH is as safe and effective as daily injections for managing AGHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a long-acting growth hormone (GH) preparation in patients with adult GH deficiency. Hoffman, AR., Biller, BM., Cook, D., et al.[2016]

Recombinant human growth hormone (r-hGH) significantly reduces visceral adipose tissue (VAT) in HIV-1-infected patients with lipodystrophy, showing a 29% reduction at 12 weeks and nearly 40% at 24 weeks, based on a study of 26 subjects.

While r-hGH treatment led to an increase in high-density lipoprotein (HDL) levels, it also caused transient and reversible side effects, which were more common in patients receiving daily doses compared to those receiving it three times a week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, open-label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy. Bickel, M., Zangos, S., Jacobi, V., et al.[2006]

In a study of 60 patients with adult growth hormone deficiency (AGHD), higher levels of visceral adipose tissue (VAT) were linked to worse metabolic health, indicating that VAT is a significant metabolic risk factor for these patients.

After one year of growth hormone treatment, patients showed a reduction in VAT and partial improvements in lipid profiles, such as increased HDL and decreased triglycerides, although glucose metabolism remained largely unchanged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body fat distribution and circulating adipsin are related to metabolic risks in adult patients with newly diagnosed growth hormone deficiency and improve after treatment. Wang, Y., Zheng, X., Xie, X., et al.[2021]

In a Phase IV study involving 103 children aged 6 to 17, Norditropin NordiFlex was found to be significantly easier to use than previous growth hormone therapy devices, with a median ease-of-use score of 7.5 (P < 0.001).

Approximately 64.4% of patients preferred Norditropin NordiFlex, and 41% were able to self-inject, indicating that this device may enhance patient autonomy and improve adherence to growth hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

User assessment of Norditropin NordiFlex(®), a new prefilled growth hormone pen: a Phase IV multicenter prospective study. Tauber, M., Jaquet, D., Jesuran-Perelroizen, M., et al.[2022]

Recent studies have shown that replacement therapy with recombinant human growth hormone (rhGH) can significantly improve health outcomes in adults with growth hormone deficiency, including reduced cardiovascular risk, better lipid profiles, and enhanced psychological well-being.

Despite these benefits, there are still unresolved issues regarding long-term treatment, such as the potential risks of malignancy and impaired glucose tolerance, indicating that somatropin therapy should be closely monitored and conducted alongside clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth hormone deficiency in adults: the role of replacement therapy. Meling, TR.[2018]

Valtropin, a new biosimilar recombinant human growth hormone, demonstrated comparable efficacy to Humatrope in increasing height velocity in children with growth hormone deficiency, with a height velocity of 11.3 cm/year for Valtropin versus 10.5 cm/year for Humatrope over one year.

Both treatments showed similar safety profiles, with no significant differences in adverse events or bone maturation acceleration, indicating that Valtropin is a safe and effective option for treating children with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency. Peterkova, V., Arslanoglu, I., Bolshova-Zubkovskaya, E., et al.[2007]

In a study of 67 Italian patients with growth hormone deficiency, Omnitrope® was found to be effective in improving health markers like insulin-like growth factor-1 levels and body composition over an average treatment duration of 45.4 months.

While 55.2% of patients experienced adverse events, none were deemed related to Omnitrope®, indicating that it is generally safe for long-term use in adults with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope&#174; in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study. Ferone, D., Profka, E., Gasco, V., et al.[2018]

Growth hormone (GH) has been effectively used for over 40 years to improve height velocity in children with growth impairments and to correct metabolic issues related to GH deficiency, supported by extensive efficacy and safety data.

While GH has a wide safety margin, it can cause side effects such as pseudotumor cerebri and hyperglycemia, necessitating careful monitoring, especially in patients with higher risks for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of growth hormone therapy in childhood. Bowlby, DA., Rapaport, R.[2008]

Children using the ZomaJet jet-delivery device for growth hormone therapy showed significantly longer persistence in treatment (599 days) compared to those using needle-based devices (535 days), indicating better adherence to therapy.

The majority of children using ZomaJet (58%) were classified as adherent, suggesting that this delivery method may improve medication-taking behaviors and potentially lead to better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintaining persistence and adherence with subcutaneous growth-hormone therapy in children: comparing jet-delivery and needle-based devices. Spoudeas, HA., Bajaj, P., Sommerford, N.[2022]

In a year-long study involving 16 children with growth hormone deficiency, both methionyl-somatotropin (Somatonorm) and recombinant-somatotropin (Genotropin) significantly improved growth rates, with no significant difference between the two treatments.

While no serious adverse effects were reported, four children treated with Somatonorm developed low levels of antibodies against growth hormone, whereas none of the children receiving Genotropin showed this response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of the treatment of growth hormone deficiency with methionine-somatotropin or recombinant somatotropin]. Dorantes-Alvarez, LM.[2006]

In a phase III study involving 70 prepubertal children with growth hormone deficiency, long-term treatment with Omnitrope (0.03 mg/kg/day) resulted in significant growth improvements over 4 years, including an average height increase of 31.1 cm.

Omnitrope was found to be safe and well tolerated, with significant increases in serum levels of IGF-1 and IGFBP-3, indicating effective stimulation of growth-related hormones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the recombinant human growth hormone Omnitrope® in the treatment of Spanish growth hormone deficient children: results of a phase III study. López-Siguero, J., Borrás Pérez, MV., Balser, S., et al.[2013]

The PATRO Adults study is a large, long-term observational study designed to assess the safety and efficacy of somatropin (Omnitrope(®)) in adults with growth hormone deficiency, involving multiple centers across Europe.

This study will provide valuable insights into the long-term effects of Omnitrope(®) on various health factors, including diabetes development, tumor recurrence, and overall quality of life, while monitoring adverse events and safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) for the treatment of adult patients with growth hormone deficiency. Beck-Peccoz, P., Minuto, F., Leal-Cerro, A., et al.[2021]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of a long-acting growth hormone (GH) preparation in patients with adult GH deficiency. [2016]

2. England pubmed.ncbi.nlm.nih.gov

A randomized, open-label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy. [2006]

3. France pubmed.ncbi.nlm.nih.gov

Body fat distribution and circulating adipsin are related to metabolic risks in adult patients with newly diagnosed growth hormone deficiency and improve after treatment. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

User assessment of Norditropin NordiFlex(®), a new prefilled growth hormone pen: a Phase IV multicenter prospective study. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Growth hormone deficiency in adults: the role of replacement therapy. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency. [2007]

7. Italy pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope&#174; in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study. [2018]

8. Israel pubmed.ncbi.nlm.nih.gov

Safety and efficacy of growth hormone therapy in childhood. [2008]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Maintaining persistence and adherence with subcutaneous growth-hormone therapy in children: comparing jet-delivery and needle-based devices. [2022]

10. Mexico pubmed.ncbi.nlm.nih.gov

[Results of the treatment of growth hormone deficiency with methionine-somatotropin or recombinant somatotropin]. [2006]

11. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of the recombinant human growth hormone Omnitrope® in the treatment of Spanish growth hormone deficient children: results of a phase III study. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) for the treatment of adult patients with growth hormone deficiency. [2021]