Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT00109473
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 52
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether taking a growth hormone (GH) drug called somatropin causes the intestine of a person with Crohn's Disease (CD) to heal faster when compared to a person with Crohn's Disease that does not receive growth hormone drug.

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease	Drug: growth hormone; Drug: cortecosteroid	Phase 2

Detailed Description

The optimal treatment goals in childhood CD include: 1) clinical remission in conjunction with mucosal healing and 2) restoration of normal growth and development. Current therapy in most cases includes induction of remission with corticosteroids followed by maintenance of remission with 6-mercaptopurine (6-MP) or mesalamine. With this approach, the goals of achieving mucosal healing with normalization of growth are not achieved in a significant number of children. GH therapy is now used in several chronic childhood diseases which are complicated by growth failure despite adequate GH secretion. These include chronic renal failure (CRF), juvenile rheumatoid arthritis (JRA), and Turner's syndrome. However, despite a comparable frequency and magnitude of permanent growth failure, the efficacy of GH therapy in this respect has not yet been determined in a controlled trial for CD. Moreover, whether GH therapy may also directly reduce disease activity and promote intestinal healing is not known. This represents a significant clinically unmet need in this patient population. Therefore, new therapeutic approaches are needed to both improve final adult height and enhance intestinal mucosal healing in children with CD.

The primary objective of this study is to determine the effect of growth hormone (GH) therapy upon colon mucosal healing in a 12 week randomized trial in children with Crohn's Disease (CD). Children with active CD will be randomized to GH + prednisone (GP) or prednisone alone (P) for a 12 week period. This study also involves a 52 week extension phase where all participants that meet eligibility will be given the opportunity to take or continue taking growth hormone for 52 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Trial of Growth Hormone Therapy in Pediatric Crohn's Disease
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Growth Hormone plus cortecosteroid Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Drug: growth hormone; Nutropin AQ 0.075mg/kg/day subcutaneously daily; Other Names: Nutropin AQ
Active Comparator: Cortecosteroids alone Cortecosteroid therapy as prescribed by the referring gastroenterologist	Drug: cortecosteroid; As prescribed by the referring gastroenterologist; Other Names: Prednisone, Entocort

Outcome Measures

Primary Outcome Measures

1. Crohn's Disease Histologic Index of Severity (CDHIS) [Baseline and 12 weeks]

   The CDHIS was developed and validated in order to determine the effect of therapies upon histologic disease activity in Crohn's Disease. It has been used to assess mucosal healing in response to infliximab and 6-MP/AZA.It contains eight items which reflect epithelial injury, mucosal inflammation, and the extent of involvement. Scores range from 0-16, with patients with moderate to severely active CD typically having scores of 6-12. It was computed by a GI pathologist. The higher the score indicates worsening of disease, the lowest score is 0 and highest possible is 16

Secondary Outcome Measures

1. Serum IGF-1 (Insulin-like Growth Factor 1)z Score [Baseline, 12 weeks, 24 weeks]

   Elevated serum IGF-1 levels have been implicated in the development of colorectal cancer, both in the general population and in patients with an excess of growth hormone production. The serum IGF-1 levels were monitored to maintain them in the physiologic range during growth hormone therapy to reduce the risk of tumorigenesis. The levels are reported as a z score, a statistical way of standardizing data. The standard deviation is the unit of measurement of the z-score. Each z score corresponds to a point in a normal distribution, describing how much a point deviates from a mean.

2. IMPACT III Score [Baseline, 12 weeks, 24 weeks]

   Health-related quality of life (QOL)was assessed using the IMPACT 111 questionnnaire. It is a self-administered 35 item questionnaire which typically takes 10-15 minutes to complete. Scores range from 0-350, with higher scores reflecting better perceived quality of life.

3. Pediatric Crohn's Disease Activity Index (PCDAI) [Baseline, 12 and 24 weeks]

   The PCDAI is a previously validated measure of clinical disease activity for children with CD. It contains three self-report items which reflect patient abdominal pain, diarrhea, and general well being; three laboratory values; height and weight velocity; and three physical examination parameters reflecting abdominal tenderness, perirectal disease, and extra-intestinal manifestations. Scores may range from 0-100. Remission is defined as 0-10, mild disease as 10-30, and moderate to severe disease as greater than 30.

4. Total Corticosteroid Use [12 weeks]

   The total corticosteroid use over 12 weeks between groups, using the unpaired t test.

5. Crohn's Disease Endoscopic Index of Severity (CDEIS) [Baseline and 12 weeks]

   Measure of mucosal disease at baseline and week 12 obtained during colonoscopy. The CDEIS score generally ranges from 0-30. A higher score indicates more severe mucosal inflammation.

6. Height Velocity [Baseline, week 12, 24 and 48]

   Height velocity was computed every 12 weeks up to week 64 and then yearly during the Maintenance study. Since 40 to 80% of children with Crohn's disease have significant growth failure at diagnosis, height velocity is used to track for changes in height. It is calculated by measuring height at two points of time and then dividing the change by the amount of time.

7. Fecal Calprotectin [At 24 and 64 weeks]

   Fecal calprotectin is a previously validated stool marker of intestinal inflammation in Crohn's Disease.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to provide written informed consent

• Age ≥ 5 years.

• Diagnosis of Crohn's disease (CD) with ileo-colonic involvement as determined by standard clinical, radiological, and pathological criteria.

• Moderate to severely active CD as defined by a PCDAI (Pediatric Crohn's Disease Activity Index) ≥ 30.

• Currently taking Prednisone or Budesonide at starting dose (not tapering)

• May continue stable doses of AZA/6-MP, methotrexate, and/or mesalamine at entry.

• For the 52 week extension, baseline bone age ≤ 12 years for girls and ≤ 13 years for boys.

• For the 52 week extension phase, remission or mild Crohn's disease as determined by a PCDAI < 30.

Exclusion Criteria:

• Acute critical illness

• Active neoplasia

• Diabetes mellitus

• History of intracranial lesion and/or neoplasia

• Severe disease requiring hospitalization for treatment

• Current therapy with infliximab as this may independently rapidly reduce clinical disease activity and promote mucosal healing

• Use of prednisone or budesonide and in tapering phase

• Family history of colorectal cancer before age 50

• Personal or familial history of familial polyposis syndrome

• Pregnancy (positive pregnancy test) prior to randomization

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated

• Participation in another simultaneous medical investigation or trial other than the Pediatric IBD (Inflammatory Bowel Disease) registry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati
• Genentech, Inc.

Investigators

• Principal Investigator: Lee Denson, M.D., Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT00109473
• Other Study ID Numbers: CCHMC IRB #: 04-12-06; IND # 71,344
• First Posted: Apr 29, 2005
• Last Update Posted: Oct 30, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Children's Hospital Medical Center, Cincinnati: Pediatric Crohn's disease; Pediatric; Crohn's Disease
• Additional relevant MeSH terms: Crohn Disease; Prednisone; Hormones

Study Results

Participant Flow

Recruitment Details	98 subjects were assessed for eligibility, 76 did not meet inclusion criteria, 21 refused to participate
Pre-assignment Detail	21 subjects enrolled, one withdrew consent prior to randomization.

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Period Title: Baseline (0 Through 12 Weeks)
STARTED	10	10
Analyzed	10	10
COMPLETED	10	9
NOT COMPLETED	0	1
Period Title: Baseline (0 Through 12 Weeks)
STARTED	10	9
Analyzed	9	9
COMPLETED	9	9
NOT COMPLETED	1	0
Period Title: Baseline (0 Through 12 Weeks)
STARTED	9	8
Analyzed	9	8
COMPLETED	5	3
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)	Total
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician	Total of all reporting groups
Overall Participants	10	10	20
Age, Customized (participants) [Number]
<=18 years	10 100%	10 100%	20 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12 (3)	13 (3)	13 (3)
Sex: Female, Male (Count of Participants)
Female	2 20%	2 20%	4 20%
Male	8 80%	8 80%	16 80%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Crohn's Disease Histologic Index of Severity (CDHIS)
Description	The CDHIS was developed and validated in order to determine the effect of therapies upon histologic disease activity in Crohn's Disease. It has been used to assess mucosal healing in response to infliximab and 6-MP/AZA.It contains eight items which reflect epithelial injury, mucosal inflammation, and the extent of involvement. Scores range from 0-16, with patients with moderate to severely active CD typically having scores of 6-12. It was computed by a GI pathologist. The higher the score indicates worsening of disease, the lowest score is 0 and highest possible is 16
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	7	8
Week 12	6	8

2. Secondary Outcome

Title	Serum IGF-1 (Insulin-like Growth Factor 1)z Score
Description	Elevated serum IGF-1 levels have been implicated in the development of colorectal cancer, both in the general population and in patients with an excess of growth hormone production. The serum IGF-1 levels were monitored to maintain them in the physiologic range during growth hormone therapy to reduce the risk of tumorigenesis. The levels are reported as a z score, a statistical way of standardizing data. The standard deviation is the unit of measurement of the z-score. Each z score corresponds to a point in a normal distribution, describing how much a point deviates from a mean.
Time Frame	Baseline, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	-0.4 (0.6)	-0.7 (0.3)
Week 12	1.8 (1)	-1 (0.3)
Week 24	3.3 (1.5)	3.8 (1)

3. Secondary Outcome

Title	IMPACT III Score
Description	Health-related quality of life (QOL)was assessed using the IMPACT 111 questionnnaire. It is a self-administered 35 item questionnaire which typically takes 10-15 minutes to complete. Scores range from 0-350, with higher scores reflecting better perceived quality of life.
Time Frame	Baseline, 12 weeks, 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	134	132
Week 12	143	136

4. Secondary Outcome

Title	Pediatric Crohn's Disease Activity Index (PCDAI)
Description	The PCDAI is a previously validated measure of clinical disease activity for children with CD. It contains three self-report items which reflect patient abdominal pain, diarrhea, and general well being; three laboratory values; height and weight velocity; and three physical examination parameters reflecting abdominal tenderness, perirectal disease, and extra-intestinal manifestations. Scores may range from 0-100. Remission is defined as 0-10, mild disease as 10-30, and moderate to severe disease as greater than 30.
Time Frame	Baseline, 12 and 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	32	33
Week 12	8	22
Week 24	9	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Plus Corticosteroid (CTX), Corticosteroid (CTX)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Total Corticosteroid Use
Description	The total corticosteroid use over 12 weeks between groups, using the unpaired t test.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Cortecosteroid	Cortecosteroids Alone
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily) growth hormone: Nutropin AQ 0.075mg/kg/day subcutaneously daily	Cortecosteroid therapy as prescribed by the referring gastroenterologist cortecosteroid: As prescribed by the referring gastroenterologist
Measure Participants	10	8
prednisone	22 (8)	28 (10)
budesonide	7 (4)	8 (3)

6. Secondary Outcome

Title	Crohn's Disease Endoscopic Index of Severity (CDEIS)
Description	Measure of mucosal disease at baseline and week 12 obtained during colonoscopy. The CDEIS score generally ranges from 0-30. A higher score indicates more severe mucosal inflammation.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	9	8
Week 12	3	6

7. Secondary Outcome

Title	Height Velocity
Description	Height velocity was computed every 12 weeks up to week 64 and then yearly during the Maintenance study. Since 40 to 80% of children with Crohn's disease have significant growth failure at diagnosis, height velocity is used to track for changes in height. It is calculated by measuring height at two points of time and then dividing the change by the amount of time.
Time Frame	Baseline, week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	5 (1)	3 (1)
Week 12	8 (1)	3 (1)
Week 24	9 (1)	7 (1)

8. Secondary Outcome

Title	Fecal Calprotectin
Description	Fecal calprotectin is a previously validated stool marker of intestinal inflammation in Crohn's Disease.
Time Frame	At 24 and 64 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)	Subjects took corticosteroid as prescribed by their physician
Measure Participants	10	10
Baseline	863	904
Week 12	868	656

Adverse Events

Arm/Group Title	Growth Hormone Plus Corticosteroid (CTX)		Corticosteroid (CTX)		Extension Phase
Arm/Group Description	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)		Subjects took corticosteroid as recommended by their physician		Eligible subjects from both group A and group B continued on growth hormone in a 52 week extension phase
All Cause Mortality
	Growth Hormone Plus Corticosteroid (CTX)		Corticosteroid (CTX)		Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Growth Hormone Plus Corticosteroid (CTX)		Corticosteroid (CTX)		Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/10 (0%)		2/17 (11.8%)
General disorders
Abdominal Pain	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Hepatobiliary disorders
Pancreatitis	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Bruising at injection site	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Other (Not Including Serious) Adverse Events
	Growth Hormone Plus Corticosteroid (CTX)		Corticosteroid (CTX)		Extension Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		10/10 (100%)		17/17 (100%)
Blood and lymphatic system disorders
ANC elevated	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Basophils elevated	1/10 (10%)	1	0/10 (0%)	0	1/17 (5.9%)	1
Decreased hematocrit	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Eosinophils elevated	0/10 (0%)	0	1/10 (10%)	1	3/17 (17.6%)	3
Ferritin decrease	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Hematocrit decreased	0/10 (0%)	0	1/10 (10%)	1	1/17 (5.9%)	1
Hematocrit elevated	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
Hemoglobin decreased	2/10 (20%)	2	3/10 (30%)	3	1/17 (5.9%)	1
Iron level decreased	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
Iron level elevated	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Leukocyte count decreased	1/10 (10%)	1	1/10 (10%)	1	0/17 (0%)	0
Lymphocyte count decreased	3/10 (30%)	3	1/10 (10%)	1	0/17 (0%)	0
Lymphocytes elevated	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Monocytes elevated	2/10 (20%)	2	2/10 (20%)	2	3/17 (17.6%)	4
RBC decreased	1/10 (10%)	1	0/10 (0%)	0	2/17 (11.8%)	2
RBC elevated	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
RDW elevated	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Sedimentation Rate Elevated	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
Segs elevated	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
Thrombocytosis	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Fatigue	1/10 (10%)	1	2/10 (20%)	2	3/17 (17.6%)	3
Eye disorders
Eye irritation	1/10 (10%)	1	1/10 (10%)	1	0/17 (0%)	0
Gastrointestinal disorders
Anal fissure	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
Anorexia	0/10 (0%)	0	1/10 (10%)	1	3/17 (17.6%)	3
Colitis	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
Constipation	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Dehydration	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Diarrhea	3/10 (30%)	3	1/10 (10%)	1	10/17 (58.8%)	11
Dyspepsia	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Enteritis	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
Fecal urgency	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
hemorrhoids	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
Nausea	2/10 (20%)	2	3/10 (30%)	3	5/17 (29.4%)	6
Vomiting	2/10 (20%)	2	3/10 (30%)	3	6/17 (35.3%)	8
Hemorrhage nasal	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Lower gastrointestinal hemorrhage	2/10 (20%)	2	0/10 (0%)	0	0/17 (0%)	0
General disorders
Fever	2/10 (20%)	3	2/10 (20%)	2	8/17 (47.1%)	8
Increased thirst	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Insomnia	1/10 (10%)	1	0/10 (0%)	0	1/17 (5.9%)	1
Weight loss	0/10 (0%)	0	1/10 (10%)	1	3/17 (17.6%)	3
Abdominal Pain	1/10 (10%)	3	1/10 (10%)	1	7/17 (41.2%)	7
Back pain	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Breast pain	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Chest pain	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Headache	1/10 (10%)	1	4/10 (40%)	4	3/17 (17.6%)	3
Joint Pain	6/10 (60%)	6	1/10 (10%)	1	3/17 (17.6%)	3
Myalgia	0/10 (0%)	0	1/10 (10%)	1	2/10 (20%)	2
Pain in extremity	2/10 (20%)	2	0/10 (0%)	0	1/17 (5.9%)	1
Pharyngolaryngeal pain	1/10 (10%)	1	2/10 (20%)	2	2/17 (11.8%)	2
Rectal pain	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Shoulder	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Cough	2/10 (20%)	2	4/10 (40%)	4	2/17 (11.8%)	2
Sinus congestion	0/10 (0%)	0	1/10 (10%)	3	1/17 (5.9%)	1
Dysuria	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Immune system disorders
Allergic Rhinitis	2/10 (20%)	2	0/10 (0%)	0	3/17 (17.6%)	3
Hypersensitivity	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Lactose intolerant	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Infections and infestations
Colitis, infectious	0/10 (0%)	0	1/10 (10%)	1	1/17 (5.9%)	1
Gastric infection	1/10 (10%)	1	0/10 (0%)	0	3/17 (17.6%)	5
Oral thrush infection	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Pharyngitis	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Sinusitis	1/10 (10%)	1	0/10 (0%)	0	1/17 (5.9%)	1
Skin Infection	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Upper respiratory infection	1/10 (10%)	1	0/10 (0%)	0	1/17 (5.9%)	1
Vaginal Infection	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Metabolism and nutrition disorders
ALT decreased	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
ALT increased	1/10 (10%)	1	0/10 (0%)	0	3/17 (17.6%)	3
AST increased	0/10 (0%)	0	0/10 (0%)	0	7/17 (41.2%)	9
Alkaline phosphate decreased	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Anion gap high	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Anti-mitochondrial antibody	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
BUN	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
BUN decreased	4/10 (40%)	5	0/10 (0%)	0	2/17 (11.8%)	2
BUN elevated	2/10 (20%)	2	0/10 (0%)	0	1/17 (5.9%)	1
Bilirubin increased	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Blood bicarbonate decreased	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Blood bicarbonate elevated	1/10 (10%)	1	0/10 (0%)	0	5/17 (29.4%)	6
Blood glucose decreased	3/10 (30%)	3	1/10 (10%)	1	0/17 (0%)	0
Blood glucose increased	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
CRP elevated	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Chloride elevated	1/10 (10%)	1	1/10 (10%)	1	2/10 (20%)	2
Creatnine decreased	4/10 (40%)	5	1/10 (10%)	1	3/17 (17.6%)	3
Creatinine elevated	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Hyperinsulinemia	0/10 (0%)	0	0/10 (0%)	0	5/17 (29.4%)	6
Serum albumin decreased	1/10 (10%)	1	1/10 (10%)	1	0/17 (0%)	0
Serum potassium decreased	3/10 (30%)	3	3/10 (30%)	3	1/17 (5.9%)	1
Serum potassium increased	0/10 (0%)	0	0/10 (0%)	0	2/17 (11.8%)	2
Serum sodium decreased	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Serum triglycerides increased	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Urine calcium decreased	0/10 (0%)	0	1/10 (10%)	1	0/17 (0%)	0
Musculoskeletal and connective tissue disorders
Fracture	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Joint disorder	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Nervous system disorders
Anxiety	1/10 (10%)	2	0/10 (0%)	0	1/17 (5.9%)	1
Concussion	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Peripheral sensory neuropathy	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Depression	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Skin and subcutaneous tissue disorders
Bruising at injection site	4/10 (40%)	5	2/10 (20%)	2	5/17 (29.4%)	9
Injection site reaction	1/10 (10%)	1	1/10 (10%)	1	0/17 (0%)	0
Insect bite	1/10 (10%)	1	0/10 (0%)	0	0/17 (0%)	0
Milia	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Rash acneiform	2/10 (20%)	2	1/10 (10%)	1	1/17 (5.9%)	1
Rash desquamating	0/10 (0%)	0	0/10 (0%)	0	3/17 (17.6%)	3
Seborrhea	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Skin hypopigmentation	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Skin striae	0/10 (0%)	0	0/10 (0%)	0	1/17 (5.9%)	1
Cushingoid	6/10 (60%)	6	2/10 (20%)	2	2/17 (11.8%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.