Growth Hormone Therapy for Pseudohypoparathyroidism

Overseen By Alexzandrea Buscarello, B.S.

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Connecticut Children's Medical Center

Must be taking: Growth hormone

Disqualifiers: No diagnosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12-15 years

600 Participants Needed

Trial Summary

What is the purpose of this trial?

We, the researchers, are following the natural history of Albright hereditary osteodystrophy. We have found that growth hormone deficiency is very common in patients with pseudohypoparathyroidism type 1A, which falls under the broader condition termed Albright hereditary osteodystrophy. Patients with pseudohypoparathyroidism type 1A typically are short and obese. Some of these patients are not short during childhood, but due to a combination of factors, they end up short as adults. We are evaluating the effect of growth hormone treatment in those patients with pseudohypoparathyroidism type 1A who are found to be growth hormone deficient (under R01 FD002568, IND 67148, which ended); those who are growth hormone sufficient and were found to have a positive clinical response to growth hormone in a prior clinical trial (under R01 FD00FD003409, IND 67148, which ended); or those who meet the criteria of idiopathic short stature or SGA. We are also evaluating neurocognitive and psychosocial functioning in participants with AHO in order to determine the specific impairments that are most common in the condition and to determine the best approach toward management. Funding source -- Growth hormone study: FDA OOPD \[R01 FD003409 (which has ended) and R01 FD002568 (which has ended)\] Cognitive/behavior: NICHD R21 HD078864 (which has ended)

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of growth hormone therapy for improving neurocognitive and psychosocial outcomes in patients with pseudohypoparathyroidism?

Research on growth hormone therapy in patients with growth hormone deficiency shows that it can improve memory and attention, suggesting potential benefits for neurocognitive function. However, the effects on overall psychological well-being and quality of life are less clear, and more studies are needed to confirm these findings in other conditions. ^{1 2 3 4 5}

Is growth hormone therapy generally safe for humans?

The safety data on growth hormone therapy in adults is limited, but studies suggest it is generally safe, with no significant changes in cognitive function or quality of life observed in adults with growth hormone deficiency after therapy. ^{1 5 6 7 8}

How does growth hormone therapy differ from other treatments for pseudohypoparathyroidism?

Growth hormone therapy is unique because it involves using a hormone that can potentially improve cognitive function and quality of life, as seen in other conditions like growth hormone deficiency and traumatic brain injury. This therapy may offer benefits beyond traditional treatments for pseudohypoparathyroidism, which typically focus on managing calcium and phosphate levels. ^{1 5 9 10 11}

Research Team

Emily L Germain-Lee, MD

Principal Investigator

Connecticut Children's Medical Ctr. and Univ. of Connecticut School of Medicine

Eligibility Criteria

This trial is for individuals aged 0.2 to 89 years with conditions like pseudohypoparathyroidism type 1A or pseudopseudohypoparathyroidism. Growth hormone treatment participants must be over 3, pre-pubertal, and meet criteria for idiopathic short stature or SGA if they are not growth hormone deficient.

Inclusion Criteria

I am between 4 and 65 years old.

I have been diagnosed with Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism.

I have been diagnosed with Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism.

Exclusion Criteria

I do not have pseudohypoparathyroidism type 1A.

I do not have a diagnosis of Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism.

I do not have a confirmed diagnosis of Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive growth hormone treatment to assess effects on height, weight, and metabolic health

12-15 years

Neurocognitive and Psychosocial Assessment

Participants undergo neurocognitive and psychosocial testing to identify specific impairments

1-2 days

1-2 visits (in-person)

Follow-up

Participants are monitored for long-term effects of growth hormone treatment and neurocognitive assessments

Ongoing

Treatment Details

Interventions

• Neurocognitive and psychosocial testing

Trial Overview The study observes the natural progression of Albright hereditary osteodystrophy and tests the effects of growth hormone in certain patients. It also assesses cognitive and psychosocial functioning to identify common impairments and management strategies.

Participant Groups

Group I: AHO:neurocognitive and pyschosocial Experimental Treatment 1 Intervention

Neurocognitive and psychosocial testing

Who Is Running the Clinical Trial?

Connecticut Children's Medical Center

Lead Sponsor

Trials

76

Recruited

30,000+

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Collaborator

Trials

93

Recruited

25,200+

UConn Health

Collaborator

Trials

218

Recruited

59,100+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

Growth hormone deficiency (GHD) is linked to reduced cognitive performance, affecting memory, processing speed, and attention in adults, as indicated by various neuropsychological assessments.

GH replacement therapy may reverse some cognitive deficits associated with GHD, although more reliable intervention studies are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocognitive function in adults with growth hormone deficiency. van Dam, PS.[2006]

Growth hormone (GH) deficiency (GHD) is linked to cognitive impairments, particularly in memory and attention, as shown by comparisons with matched controls.

Treatment with GH has been associated with improvements in cognitive function in individuals with GHD, indicating that GH therapy may help alleviate some cognitive deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive function in growth hormone deficiency and growth hormone replacement. Maruff, P., Falleti, M.[2006]

Growth hormone (GH) replacement therapy over 2 years significantly improves memory function in adults with childhood-onset growth hormone deficiency (CO-GHD), particularly with supraphysiological doses that accelerate recovery.

Despite improvements in memory, GH treatment does not affect psychological well-being or perceptual-motor skills, indicating that its cognitive benefits are specific to memory enhancement rather than overall psychological health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive changes during growth hormone replacement in adult men. Deijen, JB., de Boer, H., van der Veen, EA.[2022]

In a study of 19 adult patients with traumatic brain injury (TBI), those with growth hormone deficiency (GHD) showed significant cognitive improvements after 3 months of growth hormone treatment combined with cognitive rehabilitation, outperforming control patients who received a placebo.

The results suggest that exogenous growth hormone administration plays a crucial role in enhancing cognitive recovery in GHD patients, as indicated by greater improvements in various cognitive measures compared to controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Reimunde, P., Quintana, A., Castañón, B., et al.[2014]

In a study of 40 men with acquired growth hormone deficiency (GHD), 18 months of growth hormone replacement therapy did not lead to significant improvements in cognitive function or quality of life, despite initial concerns about memory performance.

The research indicates that acquired GHD in adult men does not significantly alter cognitive abilities, and low-dose GH therapy does not provide the expected benefits in cognitive function or overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency. Baum, HB., Katznelson, L., Sherman, JC., et al.[2007]

In a 10-year follow-up study involving 2,348 patients with adult growth hormone deficiency (AGHD), GH replacement therapy (GHRT) showed similar clinical outcomes in both older (≥60 years) and middle-aged (35-<60 years) patients, with effective increases in IGF-I levels for both groups.

There was no significant increase in the risk of nonserious or serious adverse reactions related to GHRT in older patients compared to middle-aged patients, although serious adverse events were more frequent in the older group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Effectiveness and Safety of GH Replacement Therapy in Adults ≥60 Years: Data From NordiNet® IOS and ANSWER. Biller, BMK., Höybye, C., Ferran, JM., et al.[2023]

Over the past 15 years, patients receiving growth hormone replacement therapy (GHR) have shown less severe growth hormone deficiency, with IGF-I standard deviation scores improving from -2.1 to -1.0 across three time intervals, indicating a shift in treatment approaches.

Patients are now starting on lower doses of growth hormone, with mean doses decreasing from 0.30 mg/day to 0.21 mg/day, which may affect treatment outcomes and highlights the need for careful consideration of changing patient characteristics in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation of the baseline characteristics and treatment parameters over time: an analysis of 15 years of growth hormone replacement in adults in the German KIMS database. Kreitschmann-Andermahr, I., Siegel, S., Francis, F., et al.[2021]

A systematic review of 94 studies indicates that both short-term and long-term growth hormone (GH) replacement therapy in adults with GH deficiency is generally safe, showing no increased risk of diabetes mellitus or cancer recurrence.

Despite the positive findings, the review highlights limitations such as the small number of subjects and insufficient long-term data, which may affect the reliability of the conclusions drawn.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reviewing the safety of GH replacement therapy in adults. Stochholm, K., Johannsson, G.[2015]

Patients with pituitary insufficiency receiving conventional hormone replacement therapy may experience negative impacts on mood, behavior, and cognitive functioning due to factors like pituitary surgery and inadequate hormone replacement regimens.

Growth hormone deficiency can significantly affect psychosocial functioning and quality of life, but growth hormone therapy may improve these outcomes, suggesting a direct effect of growth hormone on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life and cognitive function in patients with pituitary insufficiency. Burman, P., Deijen, JB.[2018]

A 6-month double-blind, randomized placebo-controlled trial involving 18 adults with growth hormone deficiency showed that long-term treatment with recombinant human growth hormone (rhGH) significantly improved attentional performance compared to placebo.

While rhGH treatment enhanced attention after 3 and 6 months, it did not lead to improvements in verbal memory or non-verbal intelligence, indicating that its cognitive benefits may be specific to attention rather than broader cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism. Oertel, H., Schneider, HJ., Stalla, GK., et al.[2013]

Growth hormone replacement therapy (GHRT) significantly improved cognitive functions and quality of life (QoL) in patients with severe traumatic brain injury (TBI) and growth hormone deficiency (GHD), based on a study of 23 treated patients compared to 27 untreated patients over one year.

The most notable cognitive improvements were seen in memory recall and specific QoL domains, particularly in patients who had lower performance levels before treatment, indicating that GHRT may be especially beneficial for those with more severe disabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth hormone replacement therapy in patients with traumatic brain injury. Moreau, OK., Cortet-Rudelli, C., Yollin, E., et al.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Neurocognitive function in adults with growth hormone deficiency. [2006]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cognitive function in growth hormone deficiency and growth hormone replacement. [2006]

3. England pubmed.ncbi.nlm.nih.gov

Cognitive changes during growth hormone replacement in adult men. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. [2014]

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

Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency. [2007]

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

Long-term Effectiveness and Safety of GH Replacement Therapy in Adults ≥60 Years: Data From NordiNet® IOS and ANSWER. [2023]

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

Variation of the baseline characteristics and treatment parameters over time: an analysis of 15 years of growth hormone replacement in adults in the German KIMS database. [2021]

8. Scotland pubmed.ncbi.nlm.nih.gov

Reviewing the safety of GH replacement therapy in adults. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Quality of life and cognitive function in patients with pituitary insufficiency. [2018]

10. England pubmed.ncbi.nlm.nih.gov

The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism. [2013]

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

Growth hormone replacement therapy in patients with traumatic brain injury. [2013]