Assessing Quality of Life Changes Using Calcitonin in Patients With Hypothyroidism on Biochemical Replacement With Levothyroxine
Phase: PHASE4
Conditions: Hypothyroidism
Sponsor: University of Maryland, Baltimore

Identifiers: NCT03342001   Unique Protocol ID: HP-
00076671 
Brief Title: Hypothyroidism Treated With Calcitonin 
 
Protocol:  11/9/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Lay Summary 
1 
* Provide a summary of the background and purpose of the study in language that can be 
understood by a person without a medical degree. 
It is known that a proportion of patients with hypothyroidism despite serum TSH levels being within the 
normal reference range, (Wiersinga, Duntas, Fadeyev, Nygaard, & Vanderpump, 2012) may continue to 
express symptoms of hypothyroidism. Common symptoms include fatigue, muscle pain, weight gain, 
and mood changes. Saravanan et al. reported in a large community-based survey that patients on 
levothyroxine even with a normal TSH showed significant impairment in psychological well-being 
compared with age- and sex-matched controls (Hospital et al., 2002). These patients are challenging to 
manage and are often unhappy with they care. 
 
Established treatment of hypothyroidism is levothyroxine. Thyroid follicular cells synthesize and secrete 
thyroxine and triiodothyronine. However, even when people are receiving adequate levothyroxine 
replacement therapy, their quality of life may not improve. Calcitonin (CT) is also produced by the 
thyroid gland, parafollicular cells. Their levels are not tested in hypothyroidism because the exact role of 
calcitonin in human health and disease is not fully known. CT has long been thought to play an 
important role in bone and mineral homeostasis, particularly with respect to its ability to regulate 
calcium metabolism. CT has been found in fish, reptiles, birds, and mammals. Salmon-derived CT is 50–
100 times more potent than human CT. Hence, salmon CT (sCT) has been used for medicinal purposes. 
 
There is a need for further research in order to understand the nature of persisting symptoms in 
patients on thyroid hormone replacement despite a serum TSH within the reference range. Calcitonin 
has been shown to alleviate pain in patients with bone or mineral disorders. To date, the use of 
calcitonin for relief of hypothyroid symptoms has not been studied. 
  
1 
* Describe the purpose, specific aims, or objectives of this research. State the hypothesis to be 
tested: 
The primary objective of our study is to evaluate the efficacy of low dose salmon calcitonin (sCT) on 
health-related quality of life in levothyroxine treated hypothyroid patients with persistent symptoms 
despite adequate biochemical correction. We hypothesize that sCT replacement will significantly reduce 
some of the hypothyroid symptoms. This is a proof of concept pilot study. 
 
-- Determine whether sCT alters plasma levels of Calcium, PO4, PTH 
-- Determine steady-state levels of CT before and after 6 weeks of treatment 
  

2 
* Discuss the research design including but not limited to such issues as: probability of group 
assignment, potential for subject to be randomized to placebo group, use of control subjects, etc.: 
This is a pilot study. Volunteer patients with hypothyroidism will be given a daily nasal spray supplement 
with salmon calcitonin 200 units, for 6 weeks. Blood samples will be taken at Day 0 (baseline) and at the 
end of 6 weeks. Thyroid, parathyroid hormone and electrolytes status will be assessed by measuring the 
levels of TSH, FT4, TT3, PTH, Calcium, Albumin, and PO4 in these samples. Participants will complete a 
quality of life survey at baseline and at 6 weeks, using a disease specific questionnaire, which was 
created to detect impaired well-being in subjects with thyroid problems. We modified items from the 
”City of hope” questionnaire (“Quality of Life -THYROID VERSION,” ). 
There will be no randomization. Adverse side effects will be recorded during the study. 
  
3 
* Describe the relevant prior experience and gaps in current knowledge. Describe any relevant 
preliminary data: 
It is known a proportion of people with hypothyroidism have persistent symptoms despite biochemical 
euthyroidism on thyroid hormone therapy. There are no good treatments currently available for such 
patients. Conflicting data exists on using T3 n this population. It is known that patients after 
thyroidectomy and many with Hashimotos have low calcitonin levels. This is a proof of concept pilot 
study to determine whether calcitonin replacement may be beneficial. 
  
4 
* Provide the scientific or scholarly background, rationale, and significance of the research and 
how it will add to existing knowledge: 
It is known that a proportion of patients with hypothyroidism despite serum TSH levels being within the 
normal reference range, (Wiersinga, Duntas, Fadeyev, Nygaard, & Vanderpump, 2012) may continue to 
express symptoms of hypothyroidism. Common symptoms include fatigue, muscle pain, weight gain, 
and mood changes. Saravanan et al. reported in a large community-based survey that patients on 
levothyroxine even with a normal TSH showed significant impairment in psychological well-being 
compared with age- and sex-matched controls (Hospital et al., 2002). These patients are challenging to 
manage and are often unhappy with they care. 
 
Established treatment of hypothyroidism is levothyroxine. Thyroid follicular cells synthesize and secrete 
thyroxine (T4) and triiodothyronine (T3). However, even when people are receiving adequate 
levothyroxine replacement therapy, their quality of life may not improve. Also, treatment with 
combined T4 and T3 has been attempted with equivocal metabolic and QoL outcomes. 
 
Calcitonin (CT) is also produced by the thyroid gland, parafollicular cells. Their levels are not tested in 
hypothyroidism because the exact role of calcitonin in human health and disease continues to be 
elucidated. It has long been thought to play an important role in bone and mineral homeostasis, 
particularly with respect to its ability to regulate calcium metabolism. CT has been found in fish, reptiles, 

birds, and mammals. Salmon-derived CT is 50–100 times more potent than human CT. Hence, salmon CT 
(sCT) has been used for medicinal purposes. Calcitonin levels have been found to be decreased in 
hypothyroidism (Poppe et al, 1999; Borges et al, 1998). 
 
To date, the use of calcitonin for relief of hypothyroid symptoms has not been studied. However, the 
use of calcitonin has shown improvements in QoL in patients with osteoporosis and osteoarthritis 
(Shohrati et al, 2015; Esenyel et al, 2013). 
  
 
1 
* Provide a summary of current literature related to the research: If you uploaded a separate 
research protocol document in the ‘Research Protocol’ page, cite the applicable section and page 
numbers from that document in the answer box below. 
Saravanan P1, Chau WF, Roberts N, Vedhara K, Greenwood R, Dayan CM. (2002). Psychological well-
being in patients on “ adequate ” doses of L -thyroxine : results of a large , controlled community- based 
questionnaire study, 577–585. 
 
Quality of Life -THYROID VERSION. (n.d.). Retrieved from http://prc.coh.org/QOL-Thy.pdf 
 
Wiersinga, W. M., Duntas, L., Fadeyev, V., Nygaard, B., & Vanderpump, M. P. J. (2012). 2012 ETA 
Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism. European Thyroid Journal, 1(2), 
55–71. https://doi.org/10.1159/000339444 
 
Poppe K, et al. Calcitonin reserve in different stages of atrophic autoimmune thyroiditis. Thyroid. 1999 
Dec;9(12):1211-4. 
 
Esenyel et al. Effects of calcitonin on knee osteoarthritis and quality of life. Reumatolo Int (2013)33:423–
427 
 
Shohrati et al. Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause Women 
Affected With Low Bone Density. Iran Red Crescent Med J. 2015 July; 17(7): e6613. 
 
Borges et al., Calcitonin deficiency in early stages of chronic autoimmune thyroiditis. Clin Endocrinol 
(Oxf). 1998 Jul;49(1):69-75. 
 

Study Procedures 
  
  
If you uploaded a separate research protocol document in the ‘Research Protocol’ page, cite the 
applicable section and page numbers from that document in the answer boxes below. (If this study is a 
collaborative UM/VA study please list each procedure that is being conducted and the locations where it 
is being conducted.) 
1 
* Describe all procedures being performed for research purposes only (these procedures would 
not be done if individuals were not in the study) and when they are performed, including procedures 
being performed to monitor subjects for safety or to minimize risks: 
-Recruit biochemical euthyroid patients with persistent symptoms of hypothyroidism and investigate the 
efficacy of calcitonin on improving quality of life. 
-Patients will be enrolled if have diagnosis of hypothyroidism and currently euthyroid on hormone 
replacement (nl TSH within 60 days of study initiation, or if not done will be drawn at first visit) 
-Patients will be provided with calcitonin spray for 6 weeks, while receiving usual clinical care. Quality of 
life will be assessed by Qol questionnaire at pre and post intervention and blood samples will be 
collected at initial visit and 6 weeks. Patient will be screened using inclusion and exclusion criteria. If 
they agree to be part of the study they will be given the questionnaire and have blood drawn (clinical 
care, if not already done within 60 days of visit) prior to distribution of calcitonin. 
-Calcitonin will be stored and dispensed by the Midtown Hospital pharmacy, which has SOP's for storing 
and dispensing study drug 
- If blood testing not available, will do screening blood tests on visit 1 and if qualify for study, will have 
separate visit to initiate calcitonin 
- If the participant has an abnormal lab value disqualifying them from the study, he/she will be informed 
and appropriate medical care will be given. Participant will not be allowed to take part in study any 
longer 
- At 3 week point will have phone interview with subject to assess for side effects and medication 
compliance 
- Handout to be given to pt to record compliance and adverse events 
-At the end of 6 weeks, all participants will return to the CDE to complete the quality of life survey again. 
Will also assess for symptoms and side effects from calcitonin and about compliance with medication. At 
this time blood will be drawn again (clinical care). 
- All subjects taking any study drug will be included in ITT analysis. If the subject misses > 30% of doses, 
will have subanalysis of subjects who took drug regularly vs. not, and will add additional participants to 
add power to outcomes. 
-All screening labs will be done after the consent is signed and screening labs will be reviewed for 
eligibility prior to the administration of the study drug. 

  
2 
* Describe all procedures already being performed for diagnostic or treatment purposes (if not 
applicable to the study, enter "N/A"): 
Blood draws 
  
3 
* Describe the duration of an individual participant's participation in the study:  
The duration of an individuals participation will be 6 weeks. 
  
4 
* Describe the amount of time it will take to complete the entire study: 
The duration of the entire study is expected to be completed in less than 2 years. 
Study collection should be finished in approximately 12 months and data analysis should take 
approximately an additional 6 months. 
  
5 
* Describe any additional participant requirements: 
Participants will not have any additional requirements that are not outlined above. 
  
Sample Size and Data Analysis 
If you uploaded a separate research protocol document in the ‘Research Protocol’ page, cite the 
applicable section and page numbers from that document in the answer boxes below. 
1 
* Provide the rationale and sample size calculations for the proposed target population: 
This is a pilot study and sample of convenience 
2 
* Provide the plan for data analysis. Include in the description the types of comparisons that are 
planned (e.g., comparison of means, comparison of proportions, regressions, analysis of variance, etc.),  
which is the primary comparison/analysis, and how the analyses proposed will relate to the primary 
purposes of the study: 
Primary outcome to be measured is mean change in QoL before and after CT. All subjects taking any 
study drug will be included in ITT analysis. If the subject misses > 30% of doses, will have subanalysis of 
subjects who took drug regularly vs. not, and will add additional participants to add power to outcomes. 
This is a pilot study to prove concept and it is understood may not be powered adequately. 
  
1 
* Describe whether results (study results or individual subject results, such as results of 
investigational diagnostic tests, genetic tests, or incidental findings) will be shared with subjects or 
others (e.g., the subject’s primary care physicians) and if so, describe how it will be shared: 

The results of the study will not be shared with the individual subjects or primary care physicians 
individually. This is a pilot study aiming to demonstrate the effects of calcitonin on quality of life in 
patients with hypothyroidism. Results may be presented at national conferences and published in peer-
reviewed journals. 
  
ID: VIEW4E02808CBD800 
Name: v2_Sharing of Results 
HP-00076671 
View: v2_Research with Drugs or Biologics 
Research with Drugs or Biologics 
You indicated on the "Type of Research" page that your study involves use of unapproved 
drug(s)/biologic(s) or approved drug(s)/biologic(s) whose use is specified in the protocol AND/OR 
evaluation of food(s) or dietary supplement(s) to diagnose, cure, treat, or mitigate a disease or 
condition. 
1 
 
* List all drugs/biologics to be administered in this study. Be sure to list each drug/biologic with its 
generic name only. 
  
Drug Name 
FDA Approved IND Number 
PI IND Holder 
View 
calcitonin 
yes 
  
no 
 
List inclusion criteria (List each Inclusion Criteria individually, using the ADD button): 
  
Number 
Criteria 
View 1 
Age 18-89 
View 2 
TSH wnl (0.4-4.5) 
View 3 
on levothyroxine therapy 
List exclusion criteria (List each Exclusion Criteria individually, using the ADD button): 
  
Number 
Criteria 
View   1   
pregnant, planning to get pregnant, or up to 6 months post partum 
View   2   
Current or previous thyroid cancer 
View   3   
Congenital hypothyroidism 
View   4   
any tobacco use 

View   5   
prescribed proton pump inhibitors 
View   6   
prescribed steroids 
View   7   
prescribed armour thyroid 
View   8   
Unstable medical conditions (CKD, Cirrhosis etc) 
View   10   
Pituitary disease 
View   11   
Hypocalcemia