Insulin-Like Growth Factor 1 for Aging Skin
Palo Alto (17 mi)Overseen byJeffrey B Travers, MD, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Wright State University
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This study does not involve any particular diagnosis. The goal of this research study is to explore the effects of artificial sunlight (ultraviolet B radiation; UVB) on the skin of young adults versus geriatric adults. Sunlight exerts many effects on the body. There is evidence that in response to ultraviolet B radiation (UVB), which are the burning rays of sunlight, young adult skin responds differently than geriatric skin. In fact, researchers feel that this difference in how the skin reacts to UVB is why skin cancers are found in older skin. Researchers believe that a major difference between young adult and geriatric skin is that young skin has a lot of a protein called insulin-like growth factor-1 (IGF-1), whereas geriatric skin has very little. The current study will test how young adult versus geriatric skin responds to UVB, and if geriatric skin treated with an injection of small amount of IGF-1 drug will then act like young skin.
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you are on photosensitizing medications, you cannot participate in the trial.
Is the drug Insulin-Like Growth Factor 1 (IGF-1) promising for aging skin?Insulin-Like Growth Factor 1 (IGF-1) is a hormone that helps with growth and tissue repair. It decreases as we age, which might contribute to changes in our skin and body. While IGF-1 has potential benefits for aging skin by possibly improving tissue regeneration, it's not yet clear if it can effectively reverse or slow down skin aging.257812
What safety data exists for IGF-1 treatment for aging skin?The safety data for IGF-1, also known as somatomedin-1, indicates that adverse effects are primarily related to overdosage. Clinical trials have been conducted for conditions like Laron syndrome and diabetes, showing benefits in growth and insulin sensitivity. However, during growth hormone treatments in elderly men with low IGF-I levels, side effects such as carpal tunnel syndrome and gynecomastia have been observed. While IGF-1 has shown potential benefits in body composition and quality of life, it can also cause significant morbidity.12346
What data supports the idea that Insulin-Like Growth Factor 1 for Aging Skin is an effective treatment?The available research shows that Insulin-Like Growth Factor 1 (IGF-1) plays a significant role in skin aging. One study found that IGF-1 can stimulate the growth of skin cells, which may help maintain skin thickness and surface lipids as we age. Another study highlighted that increasing IGF-1 levels in aged skin through treatments like fractionated laser resurfacing can reduce the risk of skin issues like actinic keratosis and nonmelanoma skin cancer. This suggests that IGF-1 is important for maintaining healthy skin as we age.29101113
Eligibility Criteria
This trial is for healthy adults aged 21-30 or 65 and older with white skin (Fitzpatrick types I and II). Participants must understand the procedures and risks. Those with allergies to lidocaine, serious health issues, on photosensitizing meds, diabetes, abnormal scarring history, skin infections, pregnancy/nursing or known photosensitivity cannot join.Inclusion Criteria
I am either between 21-30 years old or 65 and older.
Exclusion Criteria
I am taking medication that increases my sensitivity to light.
I have had skin infections in the past.
I have diabetes.
Treatment Details
The study investigates how young adult versus geriatric skin responds to artificial sunlight (UVB). It will test if treating geriatric skin with an injection of IGF-1 makes it respond like young skin. The intervention includes exposure to UVB and possibly receiving an IGF-1 injection.
2Treatment groups
Active Control
Placebo Group
Group I: Geriatric AdultActive Control1 Intervention
Four small areas will undergo injection of a small amount of IGF-1 drug and two will undergo injections with saline. Then the injected areas will be treated with a small amount of UVB.
Group II: Young AdultPlacebo Group1 Intervention
One small area of skin will undergo treatment with a small amount of UVB.
No Insulin-Like Growth Factor 1 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as IGF-1 for:
- Growth hormone deficiency
- Short stature
🇪🇺 Approved in European Union as Somatomedin C for:
- Growth hormone deficiency
- Short stature
Find a clinic near you
Research locations nearbySelect from list below to view details:
Wright State PhysiciansFairborn, OH
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Who is running the clinical trial?
Wright State UniversityLead Sponsor
Jeffrey B. Travers, MD, PhDLead Sponsor
References
Effects of human growth hormone on body composition in elderly men. [2018]Body composition changes progressively in mid and late adulthood. Lean body mass in men over 50 years old contracts at an average rate of -0.6% per year. Body weight tends to remain stable because of a reciprocal expansion of adipose mass. The shrinkage of the lean body mass reflects the atrophy of skeletal muscles, skin and visceral organs. Because growth hormone causes expansion of the lean body mass and contraction of the adipose mass, and because growth hormone secretion tends to diminish in late adulthood, it has been postulated that geriatric hyposomatotropism is a contributory cause to the body composition changes described above. The authors have tested this hypothesis by recruiting 45 independent men over 61 years old with plasma somatomedin C level below 0.35 U/ml, indicating little or no detectable growth hormone secretion. The 21-month protocol was as follows: baseline period 0-6 months, experimental period 6-18 months and post-experimental period 18-21 months. During the experimental period, 26 men (group I) received approximately 0.03 mg/kg of biosynthetic human growth hormone (hGH) subcutaneously 3 times a week, while 19 men (group II) received no treatment. Plasma somatomedin C was measured monthly. The following outcome variables were measured at 0, 6, 12 and 18 months: lean body mass, adipose mass, skin thickness (dermis plus epidermis), sizes of the liver, spleen and kidneys, the cross sectional areas of ten muscle groups, and bone density at 9 skeletal sites. Lean body mass and adipose mass were also measured at 21 months. In group I, hGH treatment raised the plasma somatomedin C level and maintained it in the range 0.5-1.5 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin-like growth factors and aging. [2018]Since its proposal three decades ago, the evidence in favor of the somatomedin hypothesis has been compelling. It is clear that somatotrophic actions of growth hormone are mediated through generation of insulin-like peptides and interaction of these peptides with plasma membrane receptors on sensitive cells. It is possible that such actions result from effects of circulating insulin-like peptides and/or insulin-like peptides generated in proximity to their sites of action (autocrine or paracrine effects). Most or all of circulating somatomedin activity in humans can be accounted for by insulin-like growth factors I and II (IFGs I and II). These peptides have considerable structural homology with insulin but, unlike insulin, they circulate in tight, noncovalent association with specific carrier protein. Levels of circulating IGF I and IGF II are affected by growth hormone, but the former peptide is the more sensitive to growth hormone. Levels of circulating IGF I in humans are low at birth, rise progressively during childhood, and peak during midadolescence. The increase in stature that occurs normally during adolescence probably results from this increase in circulating IGF I. Following adolescence, levels of circulating IGF I fall progressively as a function of age. There is good evidence that the reduction in levels of circulating IGF I is related to decreased secretion of growth hormone that accompanies aging. Although it has been suggested that decreased function of the growth hormone-somatomedin axis may cause changes in anabolic indices that accompany the aging process, definitive proof for this hypothesis is lacking. In contrast to IGF I, circulating IGF II reaches "adult" levels early in childhood, and changes are relatively small as a function of increasing age. Counterparts of IGF I and IGF II are present in rats. Dynamics of the growth hormone-somatomedin axis are similar in rats and humans for IGF I. In contrast, levels of IGF II in rat fall precipitously following birth, suggesting a role for rat IGF II in fetal growth and development. The rat has been used as an experimental animal to define the role of the growth hormone-somatomedin axis in aging. As in human studies, no firm relationship between somatomedins and aging has been established in the rat.
Carpal tunnel syndrome and gynaecomastia during growth hormone treatment of elderly men with low circulating IGF-I concentrations. [2019]We studied the relationship between plasma level of insulin-like growth hormone I (IGF-I), changes in lean body mass and in adipose mass, and adverse side-effects during human growth hormone (hGH) treatment of elderly men who had low IGF-I levels.
Functional consequences of the somatopause and its treatment. [2022]The decline in the function of the growth hormone-releasing hormone, growth hormone, insulin-like growth factor (GHRH-GH-IGF) axis has been termed the somatopause. Many of the catabolic sequelae seen in normal aging has been attributed to this decrease in circulating GH and IGF-I. In order to provide hormone replacement therapy for the somatopause, elderly subjects have been treated with GH, IGF-I, or both hormones together. Whereas numerous beneficial effects on body composition, strength, and quality of life have been reported in some studies, other studies have reported only marginal functional improvements. Moreover, it is clear that both hormones can cause significant morbidity.
Insulin-Like growth factor I: implications in aging. [2018]According to the somatomedin model, growth hormone (GH)-dependent hepatic synthesis is responsible for maintaining circulating insulin-like growth factor (IGF)-I levels. On the other hand, the local autocrine/paracrine IGF-I expression in peripheral tissue is generally GH-independent and reflects the effects of various and tissue-specific trophic hormones. Circulating IGF-I levels undergo important age-related variations increasing at puberty and decreasing, thereafter, to low levels in the elderly. Low IGF-I levels in the elderly mainly reflect impaired somatotroph secretion but the decline in gonadal sex steroid levels, some protein and micronutrients malnutrition as well as age-dependent variations in IGF-binding proteins may also play a role in the age-related decrease in IGF-I activity. This, in turn, partially accounts for age-related changes in bones, muscles, cardiovascular system, central nervous system and the immune system. However, it is currently unclear whether treatment with exogenous IGF-I can retard or reverse age-related changes in body structure and function.
Clinical use of somatomedin-1: yes or no? [2018]Insulin-like growth factor-I (IGF-I) is a polypeptide of 70 amino acids. The circulatory form of IGF-I is synthesised in the liver. The metabolic activity of IGF-I is regulated by 6 IGF binding proteins. the most important being IGF binding protein-3. IGF-I acts via its own receptor, which resembles that of insulin. It has been demonstrated that the effects of pituitary growth hormone (GH, somatropin) on protein metabolism, including growth and effects on nervous and renal tissue, are mediated by IGF-I, whereas these 2 hormones are antagonistic in their effects on insulin and some aspects of lipid metabolism. The biosynthesis of recombinant human IGF-I (somatomedin-1) in 1986 enabled the initiation of clinical trials. The most important involves replacement therapy in primary IGF-I deficiency, such as Laron syndrome (primary GH resistance or insensitivity), and in patients who have developed antibodies to human GH. In Laron syndrome, which is characterised by dwarfism, somatomedin-1 stimulates growth and increases muscle and bone mass, as well as normalising blood chemistry. In diabetes mellitus types 1 and 2 (insulin-dependent and non-insulin-dependent), somatomedin-1 increases the sensitivity to insulin and improves glucose utilisation, and may contribute to healing of injured nerve tissue and improve renal function in humans. Adverse effects of somatomedin-1 appear to be related to overdosage. In conclusion, somatomedin-1 is an important hormone which has clinical roles as replacement therapy and other pharmacological therapies.
Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein. [2019]It is well documented that serum insulin-like growth factor 1 (IGF-1) levels as well as growth hormone secretion decline with advancing age. Low levels of IGF-1 are shown to be associated with low activity of growth hormone, low lean mass, and high body fat mass; however, in the elderly, the relationship has not been confirmed.
[Insulin-like growth factor 1 (somatomedin C) and its binding proteins 1 and 3 in children with special consideration of diabetes]. [2006]Insulin-like growth factor 1 (IGF-1, somatomedin C) belongs to a family of polypeptide hormones, which are structurally close relatives of insulin. Circulating IGF-1 is synthesised in the liver. Serum level of somatomedin is regulated by: growth hormone (GH), insulin and nutrition. It is also produced locally by most tissues, where it acts in auto- and paracrine manner. IGF-1 takes part in regulating growth after binding to IGF receptor during embryonic development and after birth. In adults somatomedin plays a role in the process of regeneration, mainly in the case of connective tissue. It is also a weak mitogen for most cultured cells and it can act like insulin. Somatomedin circulates in plasma in complex with a family of binding proteins. 85-95% of total IGF-1 is found in the complex consisting of IGF-1, binding protein 3 and ALS. This complex is a store of IGF and limits the access of somatomedin to specific receptors. After binding with IGFBP-1, IGFBP-2 and IGFBP-6, IGF-1 passes through epithelium and reaches the target cells. The serum concentration of this protein appears to be inversely related to insulin level. IGFBP-1 can modulate IGF growth-promoting effect. IGF and its binding proteins are important in the diagnosis and treatment of some pituitary diseases, catabolic states such as malnutrition, burns, AIDS, polytrauma and tumors with hypoglikemia. Insulin-like growth factors may be involved in the etiopathogenesis of diabetes and in diabetes complications. Abnormalities in functioning of GH-IGF-1 axis are regarded as a cause of the growth retardation in children with poor metabolic control of type 1 diabetes, insulin-resistance, dawn phenomenon and fat disorders. rhIGF has been used in the treatment of some diseases bringing positive results.
Plasma IGF-I levels and cognitive performance in older women. [2016]Emerging biologic and epidemiologic evidence suggests benefits of insulin-like growth factor-I (IGF-I) in cognitive aging.
Interplay of IGF-I and 17beta-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro. [2013]In order to obtain greater insights into the molecular mechanisms accompanying hormonal aging the effects of growth hormone (GH), insulin-like growth factor-I (IGF-I), 17beta-estradiol, progesterone and dehydroepiandrosterone were tested as single agents in concentrations corresponding to 20- and 60-year-old females on human SZ95 sebocytes and fibroblasts. Cell proliferation and viability were measured by 4-methylumbelliferyl heptanoate and lactate dehydrogenase microassays, respectively, whereas lipid accumulation was documented via nile red microassay and fluorescence microscopy. mRNA and protein expression were evaluated via real-time RT-PCR and Western blotting or ELISA, accordingly. Our results depict the importance of IGF-I for lipid synthesis in SZ95 sebocyte and demonstrate the lack of 17beta-estradiol, dehydroepiandrosterone and progesterone activity on lipid synthesis and SZ95 sebocyte proliferation suggesting that the action of these hormones in vivo may be implemented through indirect pathways. Fibroblast showed to be more susceptible to 17beta-estradiol treatment, while IGF-I could significantly stimulate fibroblast proliferation in a dose-dependent manner. Furthermore, an interplay between the 17beta-estradiol and IGF-I signaling pathway was documented in both cell types. In conclusion, IGF-I is a key regulator of human skin aging and declining IGF-I levels with age may play a significant role in the reduction of skin surface lipids and thickness.
Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies. [2021]Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.
Clinical relevance of insulin-like growth factor-1 to cardiovascular risk markers. [2022]Insulin-like growth factor-1 (IGF-1) is an anabolic hormone, the levels of which decline with age. The present study aimed to determine the impact of age-related declines in serum IGF-1 levels on various physiological processes.
Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia. [2023]BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.