Growth Hormone Therapy for Pseudohypoparathyroidism
Recruiting in Palo Alto (17 mi)
Overseen byEmily L Germain-Lee, MD
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Connecticut Children's Medical Center
Must be taking: Growth hormone
Disqualifiers: No diagnosis, others
No Placebo Group
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.
12345Is 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.
15678How 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.
1591011Eligibility 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.
+4 more
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.
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: AHO:neurocognitive and pyschosocialExperimental Treatment1 Intervention
Neurocognitive and psychosocial testing
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Connecticut Children's Medical CenterHartford, CT
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Who Is Running the Clinical Trial?
Connecticut Children's Medical CenterLead Sponsor
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.Collaborator
UConn HealthCollaborator
Johns Hopkins UniversityCollaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
References
Neurocognitive function in adults with growth hormone deficiency. [2006]The clinical condition of growth hormone deficiency (GHD) as a consequence of pituitary or hypothalamic disease has been associated with reduced cognitive performance. In several studies, neuropsychological assessment has been performed in adults with GHD both before and after growth hormone (GH) replacement therapy. Interpretation of the available data is complicated by the variation in patient selection as well as the neuropsychological tests used in such studies. Most of the available studies indicate that GHD can lead to small, but clinically relevant changes in memory, processing speed and attention. Some of these changes may be reversed by GH replacement, although the number of reliable intervention studies is limited. In addition to the possible clinical relevance of neuropsychological improvement following GH replacement in patients with GHD, the observed findings may be of interest for studies in neurocognitive performance in other conditions associated with changes in the activity of the somatotrophic axis, and in the understanding of underlying pathophysiological mechanisms.
Cognitive function in growth hormone deficiency and growth hormone replacement. [2006]There is converging evidence from neuropsychological studies that growth hormone (GH) is associated with cognitive function. The aim of the current study was to review the existing neuropsychological literature for studies in which cognitive assessment had been conducted in patients with GH deficiency (GHD), and where change in cognitive function had been assessed following treatment with GH. Studies that have investigated relationships between GH and cognitive function and those that have developed methodological and statistical approaches that could be useful in future GH studies were identified. In this review, GH levels were found to be associated with cognitive function. Untreated individuals with GHD showed reliable impairment in memory and attentional functions when compared with matched controls. Appropriately designed prospective studies also indicated that cognitive function improved with GH treatment. It was concluded that individuals with GHD do show cognitive impairment and that this is ameliorated to some extent by GH treatment. It is now important to establish the clinical importance of these findings, and further work is required to understand better the nature, magnitude and meaning of GH-related cognitive impairments and improvements.
Cognitive changes during growth hormone replacement in adult men. [2022]The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.
Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. [2014]To assess the effects of growth hormone (GH) treatment combined with cognitive rehabilitation in patients with adult growth hormone deficiency (GHD) and cognitive disorders occurring after traumatic brain injury (TBI).
Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency. [2007]GH replacement of adults with acquired GH deficiency (GHD) results in body composition changes including increases in lean mass and bone mineral density. However, the effects of long-term GH therapy on cognitive function are largely unknown, and there are conflicting data regarding quality of life. We performed a randomized, double-blind, placebo-controlled study of GH replacement in adults with GHD and measured cognition and sense of well-being using standardized psychometric tests before and after therapy. Forty men (median age 51 yr, range 24-64 yr) with a history of pituitary disease were randomized to GH therapy (starting dose, 10 +/- 0.3 micrograms/kg per day: mean treatment dose, 4 +/- 2 micrograms/kg per day) vs. placebo for 18 months, and GH doses were adjusted according to serum insulin growth factor-I levels. At baseline, the patients displayed a full-scale intelligence quotient (IQ) score nearly 1 SD above the normal mean. Mean scores on all cognitive tests fell within normal limits, and on many tests, fell above the mean. On tests of verbal learning and delayed visual memory, mean test scores fell below the mean (although within normal limits), suggestive of a relative compromise in the area of memory performance. Following 18 months of GH replacement therapy, there were no significant changes in cognitive function or quality of life. We conclude that acquired GHD in adult men is not associated with significant alterations in cognitive function as assessed by standardized tests, and chronic low-dose GH replacement therapy does not result in significant beneficial effects on cognitive function or quality of life. Although previous studies have suggested that GH replacement in adults with acquired GHD may improve quality of life, our data do not support the use of physiological GH replacement in GHD men for this indication.
Long-term Effectiveness and Safety of GH Replacement Therapy in Adults ≥60 Years: Data From NordiNet® IOS and ANSWER. [2023]Effectiveness and safety data on GH replacement therapy (GHRT) in older adults with adult GH deficiency (AGHD) are limited.
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]The purpose of this study is to examine potential implications of changes in the approach to adult growth hormone (GH) replacement (GHR) over the last 15 years. Therefore, we analysed the German KIMS database as one of the largest single country pharmacoepidemiological databases on adult GH deficiency (GHD). Based on the date of their first GH application patients were assigned to three intervals (1995-1999, 2000-2004, 2005-2009). A multivariate analysis of variance with interval and sex as independent variables was conducted. Differences were analysed with respect to IGF-I standard deviation score (SDS), quality of life, latency between GHD diagnosis and first GH dose, body mass index, waist-hip ratio, lipid profile, and GH dose. All analyses were conducted at baseline, 1 year, and 3 years of GHR. We detected significant associations between time interval and patient characteristics at baseline and with treatment effects. Recently, patients with less severe GHD (mean IGF-I SDS: -2.1, -1.6, -1.0 in the 1st, 2nd and 3rd interval; p = 0.000) are treated with lower GH starting doses (mean 0.30, 0.19, 0.21 mg/day in the 1st, 2nd and 3rd interval; p = 0.000). In the first time interval, IGF-I SDS was not normalized in females after 3 years of GHR. The results of our analysis demonstrate prominent changes in patient characteristics and handling of GHR. They highlight that approach to therapy and patient inclusion criteria change over time and may represent an important confounder for any analysis in epidemiological surveillance surveys.
Reviewing the safety of GH replacement therapy in adults. [2015]Systematic data on safety of growth hormone (GH) replacement therapy in adult GH deficiency is lacking.
Quality of life and cognitive function in patients with pituitary insufficiency. [2018]This review is concerned with the psychosocial functioning and the quality of life in patients with pituitary insufficiency who are receiving conventional hormone replacement therapy. The possible negative effects of pituitary surgery, treatment with irradiation, and suboptimal replacement regimens with hormones other than growth hormone on mood, behaviour and cognitive functioning are discussed. The influence of growth hormone deficiency per se, and the outcome of growth hormone therapy in adult patients are addressed in detail. A possible mechanism for a direct effect of growth hormone on the brain is presented.
The effect of growth hormone substitution on cognitive performance in adult patients with hypopituitarism. [2013]Adult hypopituitary patients with growth hormone deficiency, though on adequate adrenal, thyroid or sex hormone replacement therapy, complain of attention and memory disabilities. During the past years several studies have evidenced that growth hormone (GH) may exert distinctive effects on the central nervous system and induce beneficial effects on psychological capabilities. The aim of our study was to determine whether a long-term replacement therapy of recombinant human growth hormone (rhGH) affects cognitive performance in adults with GH deficiency.
Growth hormone replacement therapy in patients with traumatic brain injury. [2013]In patients with severe traumatic brain injury (TBI), a growth hormone deficiency (GHD) is frequent and may contribute to the cognitive sequelae and reduction in quality of life (QoL). Recent studies have suggested that GH replacement therapy (GHRT) can improve processing speed and memory. The aim of the study was to analyze the efficacy of GHRT on cognition, activities of daily living (ADL), and QoL and the factors that predicted and contributed to these effects. We included patients at least 1 year after their TBI and assessed pituitary functions (with stimulation tests), cognition (attention, memory, and executive function), participation in ADL and QoL. GHD was treated for at least 1 year in 23 patients, who were compared with 27 non-treated patients. Other deficiencies were also treated. Measurements were performed at baseline and 1 year later. An analysis of variance of the factors group and session (p ≤ 0.05) showed that most cognitive parameters had improved at 1 year (evidencing a session effect). A stronger effect of GHRT (i.e. a group x session interaction) was found for Rey Osterrieth complex figure recall and 2/6 domains in the QoL questionnaire ("personal" and "functional"). Trends (p ≤ 0.07) were also found for spatial orientation and immediate recall in the verbal memory test. Greatest improvements were associated with lower performance before treatment. The magnitude of the improvements in ADL and QoL was moderately correlated with the improvement in cognition. In conclusion, replacement therapy can improve cognition and QoL in patients with TBI who have GHD, especially in those with severe disabilities.